Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2022 Volume 24 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2022 Volume 24 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

  • Authors:
    • Ruizhu Sun
    • Zhansheng Hou
    • Yankui Zhang
    • Bo Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Medical Care, The Third Affiliated Hospital of Kunming Medical University, College of Clinical Oncology, Kunming Medical University, Kunming, Yunnan 650500, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 408
    |
    Published online on: September 26, 2022
       https://doi.org/10.3892/ol.2022.13528
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

According to global cancer data, lung cancer was the leading cause of cancer‑related death in 2020. With the diversification of treatment strategies, the survival outcomes of patients with advanced lung cancer have improved significantly, but the 5‑year overall survival rate remains <20%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) are the preferred treatment for lung adenocarcinoma patients with EGFR‑sensitive mutations; however, acquired drug resistance is inevitable. Osimertinib (a third‑generation EGFR inhibitor) is the most commonly used drug for cancers with a secondary T790M mutation. Unfortunately, acquired drug resistance against third‑generation drugs still emerges. The C797s mutation is the primary acquired resistance mechanism against Osimertinib. Research on fourth‑generation EGFR‑TKI drugs with a C797s mutation is currently at various experimental stages, and no drug has been approved for clinical use. In addition to the resistance mechanisms described above, HER2 amplification, MET amplification, PIK3A mutation, KRAS mutation, BRAF mutation, transformation to small cell lung cancer, transformation to lung squamous cell carcinoma, and EMT have been reported as mechanisms of acquired drug resistance to first‑, second‑ and third‑generation EGFR‑TKIs. These mechanisms are noted in a relatively high proportion of tumors, but treatment options are limited. In recent years, immunotherapy has made progress in the treatment of several cancers, including advanced EGFR‑mutated non‑small cell lung cancer (NSCLC). Due to the relatively high frequency of EGFR mutation in patients with lung adenocarcinoma in China, an increased number of patients develop EGFR‑TKI resistance, and subsequent treatment options are critical. This article reviews the mechanisms of drug resistance to different EGFR‑TKIs and treatment progression, providing ideas for the follow‑up treatment for EGFR‑resistant patients.
View Figures

Figure 1

Figure 2

View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Cao M, Li H, Sun D and Chen W: Cancer burden of major cancers in China: A need for sustainable actions. Cancer Commun (Lond). 40:205–210. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Camidge DR, Doebele RC and Kerr KM: Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC. Nat Rev Clin Oncol. 16:341–355. 2019. View Article : Google Scholar

4 

Lee CK, Davies L, Wu YL, Mitsudomi T, Inoue A, Rosell R, Zhou C, Nakagawa K, Thongprasert S, Fukuoka M, et al: Gefitinib or erlotinib vs chemotherapy for EGFR mutation-positive lung cancer: Individual patient data meta-analysis of overall survival. J Natl Cancer Inst. 109:2017. View Article : Google Scholar

5 

Rotow J and Bivona TG: Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer. 17:637–658. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Kobayashi Y and Mitsudomi T: Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci. 107:1179–1186. 2016. View Article : Google Scholar

7 

Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G and Yang PC: A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 9:154–162. 2014. View Article : Google Scholar

8 

Shi Y, Li J, Zhang S, Wang M, Yang S, Li N, Wu G, Liu W, Liao G, Cai K, et al: Molecular Epidemiology of EGFR mutations in asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology-Mainland China Subset analysis of the PIONEER study. PLoS One. 10:e01435152015. View Article : Google Scholar : PubMed/NCBI

9 

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, et al: First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: Analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 26:1883–1889. 2015. View Article : Google Scholar

11 

Schuler M, Paz-Ares L, Sequist LV, Hirsh V, Lee KH, Wu YL, Lu S, Zhou C, Feng J, Ellis SH, et al: First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders in the LUX-Lung 3, 6, and 7 trials. Lung Cancer. 133:10–19. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, et al: Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): A randomised, open-label, phase 3 trial. Lancet Oncol. 18:1454–1466. 2017. View Article : Google Scholar

13 

Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, et al: Overall survival with osimertinib in untreated, EGFR-Mutated advanced NSCLC. N Engl J Med. 382. pp. 41–50. 2020, View Article : Google Scholar : PubMed/NCBI

14 

Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, et al: First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): A phase 3, open-label, randomized study. Ann Oncol. 28:2443–2450. 2017. View Article : Google Scholar

15 

Rebuzzi SE, Alfieri R, La Monica S, Minari R, Petronini PG and Tiseo M: Combination of EGFR-TKIs and chemotherapy in advanced EGFR mutated NSCLC: Review of the literature and future perspectives. Crit Rev Oncol Hematol. 146:1028202020. View Article : Google Scholar

16 

Huang L and Fu L: Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B. 5:390–401. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, et al: Osimertinib or platinum-pemetrexed in EGFR T790M-Positive lung cancer. N Engl J Med. 376:629–640. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, et al: Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 21:560–562. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Wang S, Tsui ST, Liu C, Song Y and Liu D: EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol. 9:592016. View Article : Google Scholar

20 

Lim SM, Syn NL, Cho BC and Soo RA: Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies. Cancer Treat Rev. 65:1–10. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Nagano T, Tachihara M and Nishimura Y: Mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and a potential treatment strategy. Cells. 7:2122018. View Article : Google Scholar

22 

Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, et al: Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): A phase 2B, open-label, randomised controlled trial. Lancet Oncol. 17:577–589. 2016. View Article : Google Scholar

23 

Jänne PA, Ou SI, Kim DW, Oxnard GR, Martins R, Kris MG, Dunphy F, Nishio M, O'Connell J, Paweletz C, et al: Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: A multicentre, open-label, phase 2 trial. Lancet Oncol. 15:1433–1441. 2014. View Article : Google Scholar

24 

Wu SG, Liu YN, Tsai MF, Chang YL, Yu CJ, Yang PC, Yang JC, Wen YF and Shih JY: The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients. Oncotarget. 7:12404–12413. 2016. View Article : Google Scholar

25 

Cabanero M, Sangha R, Sheffield BS, Sukhai M, Pakkal M, Kamel-Reid S, Karsan A, Ionescu D, Juergens RA, Butts C and Tsao MS: Management of EGFR-mutated non-small-cell lung cancer: Practical implications from a clinical and pathology perspective. Curr Oncol. 24:111–119. 2017. View Article : Google Scholar

26 

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, et al: Updated overall survival in a randomized study comparing dacomitinib with gefitinib as first-line treatment in patients with advanced non-small-cell lung cancer and EGFR-Activating mutations. Drugs. 81:257–266. 2021. View Article : Google Scholar : PubMed/NCBI

27 

Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, et al: Osimertinib in untreated EGFR-Mutated advanced non-small-cell lung cancer. N Engl J Med. 378:113–125. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, et al: CNS efficacy of osimertinib in patients with T790M-Positive advanced non-small-cell lung cancer: Data from a Randomized phase III Trial (AURA3). J Clin Oncol. 36:2702–2709. 2018. View Article : Google Scholar

29 

Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, et al: CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-Mutated advanced non-small-cell lung cancer. J Clin Oncol. Aug 28–2018.(Epub ahead of print). View Article : Google Scholar

30 

Lu S, Wang Q, Zhang G, Dong X, Yang CT, Song Y, Chang GC, Lu Y, Pan H, Chiu CH, et al: Efficacy of aumolertinib (HS-10296) in patients with advanced EGFR T790M+ NSCLC: Updated post-national medical products administration approval results from the APOLLO registrational trial. J Thorac Oncol. 17:411–422. 2022. View Article : Google Scholar

31 

Lu S, Wang Q, Zhang G, Dong X, Yang C, Song Y, Chang GC, LU Y, Pan H, Chiu CH, et al: 1208P Final results of APOLLO study: Overall survival (OS) of aumolertinib in patients with pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Ann Oncol. 32:S9622021. View Article : Google Scholar

32 

Shi Y, Hu X, Zhang S, Lv D, Wu L, Yu Q, Zhang Y, Liu L, Wang X, Cheng Y, et al: Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: A phase 2b, multicentre, single-arm, open-label study. Lancet Respir Med. 9:829–839. 2021. View Article : Google Scholar : PubMed/NCBI

33 

Deeks ED: Furmonertinib: First approval. Drugs. 81:1775–1780. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Ahn MJ, Han JY, Kim SW, Ki Hyeong Lee5, Kim DW, Lee YG, Cho EK, Lee GW, Lee JS, Kim JH, et al: Lazertinib, a 3rd generation EGFR-TKI, in patients with EGFR-TKI resistant NSCLC: Updated results of phase I/II Study. Abstract #9037. May 31-June 4. 2019.

35 

Kim SW, Ahn MJ, Han JY, Lee KH, Cho EK, Lee YG, Kim DW, Kim JH, Lee JS, Lee GW, et al: Intracranial anti-tumor activity of lazertinib in patients with advanced NSCLC who progressed after prior EGFR TKI therapy: Data from a phase I/II study. Am Soc Clin Oncol. 38:95712020. View Article : Google Scholar

36 

Dhillon S: Lazertinib: First approval. Drugs. 81:1107–1113. 2021. View Article : Google Scholar : PubMed/NCBI

37 

Kim ES: Olmutinib: First global approval. Drugs. 76:1153–1157. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Kim DW, Lee DH, Han JY, Lee J, Cho BC, Kang JH, Lee KH, Cho EK, Kim JS, Min YJ, et al: Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial. Lung Cancer. 135:66–72. 2019. View Article : Google Scholar : PubMed/NCBI

39 

Park K, Jӓnne PA, Kim DW, Han JY, Wu MF, Lee JS, Kang JH, Lee DH, Cho BC, Yu CJ, et al: Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study. Cancer. 127:1407–1416. 2021. View Article : Google Scholar : PubMed/NCBI

40 

Tan DS, Leighl NB, Riely GJ, Yang JC, Sequist LV, Wolf J, Seto T, Felip E, Aix SP, Jonnaert M, et al: Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: A multicentre, open-label, phase 1 study. Lancet Respir Med. 8:561–572. 2020. View Article : Google Scholar : PubMed/NCBI

41 

Costa DB, Schumer ST, Tenen DG and Kobayashi S: Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol. 26:1182–1184; author reply 1184–1186. 2008. View Article : Google Scholar

42 

Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, et al: Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 12:6494–6501. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA and Pao W: Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res. 14:7519–7525. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Grolleau E, Haddad V, Boissière L, Falchero L and Arpin D: Clinical efficacy of osimertinib in a patient presenting a double EGFR L747S and G719C mutation. J Thorac Oncol. 14:e151–e153. 2019. View Article : Google Scholar

45 

Chiba M, Togashi Y, Bannno E, Kobayashi Y, Nakamura Y, Hayashi H, Terashima M, De Velasco MA, Sakai K, Fujita Y, et al: Efficacy of irreversible EGFR-TKIs for the uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A. BMC Cancer. 17:2812017. View Article : Google Scholar : PubMed/NCBI

46 

Zhu Y, Tang J, Li X, Qin T and Wei Y: Durable response to osimertinib in a Chinese patient with metastatic lung adenocarcinoma harboring a rare EGFR L858R/D761Y compound mutation. Onco Targets Ther. 13:10447–10451. 2020. View Article : Google Scholar : PubMed/NCBI

47 

Zhang L, Yang X, Ming Z, Shi J, Lv X, Li W, Yuan B, Chen Y, Liu B, Qin K, et al: Molecular characteristics of the uncommon EGFR Exon 21 T854A Mutation and response to osimertinib in patients with non-small cell lung cancer. Clin Lung Cancer. 23:311–319. 2022. View Article : Google Scholar : PubMed/NCBI

48 

Patil T, Mushtaq R, Marsh S, Azelby C, Pujara M, Davies KD, Aisner DL, Purcell WT, Schenk EL, Pacheco JM, et al: Clinicopathologic characteristics, treatment outcomes, and acquired resistance patterns of atypical EGFR mutations and HER2 alterations in stage IV non-small-cell lung cancer. Clin Lung Cancer. 21:e191–e204. 2020. View Article : Google Scholar : PubMed/NCBI

49 

Riudavets M, Sullivan I, Abdayem P and Planchard D: Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open. 6:1002602021. View Article : Google Scholar : PubMed/NCBI

50 

Takezawa K, Pirazzoli V, Arcila ME, Nebhan CA, Song X, de Stanchina E, Ohashi K, Janjigian YY, Spitzler PJ, Melnick MA, et al: HER2 amplification: A potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2:922–933. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Elamin YY, Robichaux JP, Carter BW, Altan M, Gibbons DL, Fossella FV, Lam VK, Patel AB, Negrao MV, Le X, et al: Poziotinib for patients With HER2 Exon 20 mutant non-small-cell lung cancer: Results from a phase II Trial. J Clin Oncol. 40:702–709. 2022. View Article : Google Scholar

52 

Song Z, Lv D, Chen SQ, Huang J, Li Y, Ying S, Wu X, Hua F, Wang W, Xu C, et al: Pyrotinib in patients with HER2-Amplified advanced non-small cell lung cancer: A prospective, multicenter, single-arm trial. Clin Cancer Res. 28:461–467. 2022. View Article : Google Scholar : PubMed/NCBI

53 

Zhou C, Li X, Wang Q, Gao G, Zhang Y, Chen J, Shu Y, Hu Y, Fan Y, Fang J, et al: Pyrotinib in HER2-Mutant advanced lung adenocarcinoma after platinum-based chemotherapy: A multicenter, open-label, single-arm, phase II Study. J Clin Oncol. 38:2753–2761. 2020. View Article : Google Scholar

54 

Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, Ulaner GA, Offin M, Feldman D, Hembrough T, et al: Ado-Trastuzumab emtansine for patients with HER2-Mutant lung cancers: Results from a phase II basket trial. J Clin Oncol. 36:2532–2537. 2018. View Article : Google Scholar

55 

Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, et al: Trastuzumab deruxtecan in HER2-Mutant non-small-cell lung cancer. N Engl J Med. 386:241–251. 2022. View Article : Google Scholar : PubMed/NCBI

56 

Koch JP, Aebersold DM, Zimmer Y and Medová M: MET targeting: Time for a rematch. Oncogene. 39:2845–2862. 2020. View Article : Google Scholar : PubMed/NCBI

57 

Pasquini G and Giaccone G: C-MET inhibitors for advanced non-small cell lung cancer. Expert Opin Investig Drugs. 27:363–375. 2018. View Article : Google Scholar : PubMed/NCBI

58 

Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 316:1039–1043. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, et al: MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA. 104:20932–20937. 2007. View Article : Google Scholar : PubMed/NCBI

60 

Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, et al: Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 3:75ra262011. View Article : Google Scholar : PubMed/NCBI

61 

Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M and Riely GJ: Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 19:2240–2247. 2013. View Article : Google Scholar : PubMed/NCBI

62 

Lai GG, Lim TH, Lim J, Liew PJ, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DP, et al: Clonal MET amplification as a determinant of tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant non-small-cell lung cancer. J Clin Oncol. 37:876–884. 2019. View Article : Google Scholar

63 

Dulak AM, Gubish CT, Stabile LP, Henry C and Siegfried JM: HGF-independent potentiation of EGFR action by c-Met. Oncogene. 30:3625–3635. 2011. View Article : Google Scholar : PubMed/NCBI

64 

Dong Y, Xu J, Sun B, Wang J and Wang Z: MET-Targeted therapies and clinical outcomes: A systematic literature review. Mol Diagn Ther. 26:203–227. 2022. View Article : Google Scholar : PubMed/NCBI

65 

Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, et al: Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-Mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol. 36:3101–3109. 2018. View Article : Google Scholar

66 

Wu YL, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J, Kim DW, Soo RA, Kim SW, Pan H, et al: Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): An open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 8:1132–1143. 2020. View Article : Google Scholar : PubMed/NCBI

67 

Sequist LV, Han JY, Ahn MJ, Cho BC, Yu H, Kim SW, Yang JC, Lee JS, Su WC, Kowalski D, et al: Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: Interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 21:373–386. 2020. View Article : Google Scholar

68 

Camidge D, Barlesi F, Goldman J, Morgensztern D, Heist R, Vokes E, Spira A, Angevin E, Su W, Hong D, Strickler J, Motwani M, Sun Z, et al: MA14. 03 EGFR M+ Subgroup of Phase 1b study of telisotuzumab vedotin (Teliso-V) plus erlotinib in c-Met+ non-small cell lung cancer. J Thor Oncol. 14:S305–S306. 2019. View Article : Google Scholar

69 

McCoach CE, Yu A, Gandara DR, Riess JW, Vang DP, Li T, Lara PN, Gubens M, Lara F, Mack PC, et al: Phase I/II study of capmatinib plus erlotinib in patients with MET-positive non-small-cell lung cancer. JCO Precis Oncol. 1:PO.20.00279. 2021.

70 

Camidge DR, Moran T, Demedts I, Grosch H, Mileham K, Molina J, Juan-Vidal O, Bepler G, Goldman JW, Park K, et al: A Randomized, open-label phase II study evaluating emibetuzumab plus erlotinib and emibetuzumab monotherapy in MET immunohistochemistry positive NSCLC patients with acquired resistance to erlotinib. Clin Lung Cancer. 23:300–310. 2022. View Article : Google Scholar : PubMed/NCBI

71 

Alqahtani A, Ayesh HSK and Halawani H: PIK3CA gene mutations in solid malignancies: Association with clinicopathological parameters and prognosis. Cancers (Basel). 12:932019. View Article : Google Scholar

72 

Wang Y, Wang Y, Li J, Li J and Che G: Clinical significance of PIK3CA gene in non-small-cell lung cancer: A systematic review and meta-analysis. Biomed Res Int. 2020:36082412020.

73 

Qiu X, Wang Y, Liu F, Peng L, Fang C, Qian X, Zhang X, Wang Q, Xiao Z, Chen R, et al: Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. Am J Cancer Res. 11:3189–3200. 2021.PubMed/NCBI

74 

Song Z, Yu X and Zhang Y: Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma. Cancer Med. 5:2694–2700. 2016. View Article : Google Scholar : PubMed/NCBI

75 

Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI

76 

Westover D, Zugazagoitia J, Cho BC, Lovly CM and Paz-Ares L: Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 29 (Suppl 1):i10–i19. 2018. View Article : Google Scholar

77 

Qu GP, Shi M, Wang D, Wu JH, Wang P, Gong ML and Zhang ZJ: Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds. BMC Pulm Med. 21:2082021. View Article : Google Scholar : PubMed/NCBI

78 

Markham AJD: Alpelisib: First global approval. Drugs. 79:1249–1253. 2019. View Article : Google Scholar : PubMed/NCBI

79 

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, et al: Sotorasib for lung cancers with KRAS p.G12C Mutation. N Engl J Med. 384:2371–2381. 2021. View Article : Google Scholar : PubMed/NCBI

80 

Tanaka N, Lin JJ, Li C, Ryan MB, Zhang J, Kiedrowski LA, Michel AG, Syed MU, Fella KA, Sakhi M, et al: Clinical acquired resistance to KRASG12C inhibition through a Novel KRAS Switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK Reactivation. Cancer Discov. 11:1913–1922. 2021. View Article : Google Scholar : PubMed/NCBI

81 

Zhang SS; Nagasaka MJLCT and Therapy, : Spotlight on Sotorasib (AMG 510) for KRASG12C positive non-small cell lung cancer. Lung Cancer (Auckl). 12:115–122. 2021.PubMed/NCBI

82 

Pratilas CA, Hanrahan AJ, Halilovic E, Persaud Y, Soh J, Chitale D, Shigematsu H, Yamamoto H, Sawai A, Janakiraman M, et al: Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 68:9375–9383. 2008. View Article : Google Scholar : PubMed/NCBI

83 

Ai X, Li Y, Chen R, Gu D and Mao Y: P59. 07 mutation profile of BRAF in Chinese non-small cell lung cancer patients. J Thorac Oncol. 16:S11492021. View Article : Google Scholar

84 

Ohashi K, Sequist LV, Arcila ME, Moran T, Chmielecki J, Lin YL, Pan Y, Wang L, de Stanchina E, Shien K, et al: Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci USA. 109:E2127–E2133. 2012. View Article : Google Scholar : PubMed/NCBI

85 

Odogwu L, Mathieu L, Blumenthal G, Larkins E, Goldberg KB, Griffin N, Bijwaard K, Lee EY, Philip R, Jiang X, et al: FDA approval summary: Dabrafenib and trametinib for the treatment of metastatic non-small cell lung cancers harboring BRAF V600E mutations. Oncologist. 23:740–745. 2018. View Article : Google Scholar

86 

Zhu C, Wei Y and Wei X: AXL receptor tyrosine kinase as a promising anti-cancer approach: Functions, molecular mechanisms and clinical applications. Mol Cancer. 18:1532019. View Article : Google Scholar : PubMed/NCBI

87 

Goyette MA and Côté JF: AXL receptor tyrosine kinase as a promising therapeutic target directing multiple aspects of cancer progression and metastasis. Cancers (Basel). 14:4662022. View Article : Google Scholar : PubMed/NCBI

88 

Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK, et al: Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 44:852–860. 2012. View Article : Google Scholar

89 

Sang YB, Kim JH, Kim CG, Hong MH, Kim HR, Cho BC and Lim SM: The Development of AXL inhibitors in lung cancer: Recent progress and challenges. Front Oncol. 12:8112472022. View Article : Google Scholar

90 

Nishio M, Okamoto I, Murakami H, Horinouchi H, Toyozawa R, Takeda M, Uno M, Crawford N, Jimbo T, Ishigami M, et al: 570P A first-in-human phase I study of the AXL inhibitor DS-1205c in combination with gefitinib in subjects with EGFR-mutant NSCLC. Ann Oncol. 31:S4882020. View Article : Google Scholar

91 

Byers LA, Gold KA and Peguero JA: Ph I/II study of oral selective AXL inhibitor bemcentinib (BGB324) in combination with erlotinib in patients with advanced EGFRm NSCLC: End of trial update. Wolters Kluwer Health; 2021, View Article : Google Scholar

92 

Xun G, Hu W and Li B: PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer. Sci Rep. 11:143182021. View Article : Google Scholar : PubMed/NCBI

93 

Ferrara MG, Martini M, D'Argento E, Forcella C, Vita E, Di Noia V, Sperduti I, Bilotta M, Ribelli M, Damiano P, et al: PTEN loss as a predictor of tumor heterogeneity and poor prognosis in patients with EGFR-mutant advanced non-small-cell lung cancer receiving tyrosine kinase inhibitors. Clin Lung Cancer. 22:351–360. 2021. View Article : Google Scholar : PubMed/NCBI

94 

Redig AJ, Capelletti M, Dahlberg SE, Sholl LM, Mach S, Fontes C, Shi Y, Chalasani P and Jänne PA: Clinical and molecular characteristics of NF1-mutant lung cancer. Clin Cancer Res. 22:3148–3156. 2016. View Article : Google Scholar : PubMed/NCBI

95 

Cheung HW, Du J, Boehm JS, He F, Weir BA, Wang X, Butaney M, Sequist LV, Luo B, Engelman JA, et al: Amplification of CRKL induces transformation and epidermal growth factor receptor inhibitor resistance in human non-small cell lung cancers. Cancer Discov. 1:608–625. 2011. View Article : Google Scholar : PubMed/NCBI

96 

Cortot AB, Repellin CE, Shimamura T, Capelletti M, Zejnullahu K, Ercan D, Christensen JG, Wong KK, Gray NS and Jänne PA: Resistance to irreversible EGF receptor tyrosine kinase inhibitors through a multistep mechanism involving the IGF1R pathway. Cancer Res. 73:834–843. 2013. View Article : Google Scholar : PubMed/NCBI

97 

Ware KE, Hinz TK, Kleczko E, Singleton KR, Marek LA, Helfrich BA, Cummings CT, Graham DK, Astling D, Tan AC and Heasley LE: A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis. 2:e392013. View Article : Google Scholar : PubMed/NCBI

98 

Attili I, Passaro A, Pisapia P, Malapelle U and de Marinis F: Uncommon EGFR compound mutations in non-small cell lung cancer (NSCLC): A systematic review of available evidence. Curr Oncol. 29:255–266. 2022. View Article : Google Scholar

99 

Hayashi T, Kohsaka S, Takamochi K, Hara K, Kishikawa S, Sano K, Takahashi F, Suehara Y, Saito T, Takahashi K, et al: Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations. Hum Pathol. 103:42–51. 2020. View Article : Google Scholar

100 

Rossi S, Damiano P, Toschi L, Finocchiaro G, Giordano L, Marinello A, Bria E, D'Argento E and Santoro A: Uncommon single and compound EGFR mutations: Clinical outcomes of a heterogeneous subgroup of NSCLC. Curr Probl Cancer. 46:1007872022. View Article : Google Scholar : PubMed/NCBI

101 

Jiang D, Fu Y, Zhou X, Li Y, Cui Y, Hong L, Jin H, Shi K, Huang F, Zhang X, et al: The prognosis of EGFR complex mutation or co-mutation with tyrosine kinase inhibitor treatment in non-small cell lung cancer. Am Soc Clin Oncol. 40:e210862022. View Article : Google Scholar

102 

Wang R, Pan S and Song X: Research Advances of EGFR-TP53 Co-mutation in advanced non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 25:174–182. 2022.(In Chinese).

103 

Wang F, Zhao N, Gao G, Deng HB, Wang ZH, Deng LL, Yang Y and Lu C: Prognostic value of TP53 co-mutation status combined with EGFR mutation in patients with lung adenocarcinoma. J Cancer Res Clin Oncol. 146:2851–2859. 2020. View Article : Google Scholar

104 

Cheng Y, Ma L, Liu Y, Zhu J, Xin Y, Liu X, Wang Y, Zhang T, Yang C, Wang S, et al: Comprehensive characterization and clinical impact of concomitant genomic alterations in EGFR-mutant NSCLCs treated with EGFR kinase inhibitors. Lung Cancer. 145:63–70. 2020. View Article : Google Scholar : PubMed/NCBI

105 

Zhang Y, Li S, Lyu Z, Cai J, Zheng N, Li Y, Xu T and Zeng H: The co-mutation of EGFR and tumor-related genes leads to a worse prognosis and a higher level of tumor mutational burden in Chinese non-small cell lung cancer patients. J Thorac Dis. 14:185–193. 2022. View Article : Google Scholar : PubMed/NCBI

106 

Li HS, Liu CM and Wang Y: Limited role of KRAS mutation in guiding immunotherapy in advanced non-small-cell lung cancer. Future Oncol. 18:2433–2443. 2022. View Article : Google Scholar

107 

Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, et al: EGFR-Mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: Clinical outcomes. J Clin Oncol. 37:278–285. 2019. View Article : Google Scholar

108 

Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, et al: RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun. 6:63772015. View Article : Google Scholar : PubMed/NCBI

109 

Lee JK, Lee J, Kim S, Kim S, Youk J, Park S, An Y, Keam B, Kim DW, Heo DS, et al: Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas. J Clin Oncol. 35:3065–3074. 2017. View Article : Google Scholar

110 

Offin M, Chan JM, Tenet M, Rizvi HA, Shen R, Riely GJ, Rekhtman N, Daneshbod Y, Quintanal-Villalonga A, Penson A, et al: Concurrent RB1 and TP53 alterations define a subset of EGFR-Mutant lung cancers at risk for histologic transformation and inferior clinical outcomes. J Thorac Oncol. 14:1784–1793. 2019. View Article : Google Scholar

111 

Mambetsariev I, Arvanitis L, Fricke J, Pharaon R, Baroz AR, Afkhami M, Koczywas M, Massarelli E and Salgia R: Small cell lung cancer transformation following treatment in EGFR-Mutated non-small cell lung cancer. J Clin Med. 11:14292022. View Article : Google Scholar : PubMed/NCBI

112 

Mc Leer A, Foll M, Brevet M, Antoine M, Novello S, Mondet J, Cadranel J, Girard N, Giaj Levra M, Demontrond P, et al: Detection of acquired TERT amplification in addition to predisposing p53 and Rb pathways alterations in EGFR-mutant lung adenocarcinomas transformed into small-cell lung cancers. Lung Cancer. 167:98–106. 2022. View Article : Google Scholar : PubMed/NCBI

113 

Song KA, Niederst MJ, Lochmann TL, Hata AN, Kitai H, Ham J, Floros KV, Hicks MA, Hu H, Mulvey HE, et al: Epithelial-to-Mesenchymal transition antagonizes response to targeted therapies in lung cancer by suppressing BIM. Clin Cancer Res. 24:197–208. 2018. View Article : Google Scholar : PubMed/NCBI

114 

Shaurova T, Zhang L, Goodrich DW and Hershberger PA: Understanding lineage plasticity as a path to targeted therapy failure in EGFR-Mutant non-small cell lung cancer. Front Genet. 11:2812020. View Article : Google Scholar

115 

Wang W, Xu C, Chen H, Jia J, Wang L, Feng H, Wang H, Song Z, Yang N and Zhang Y: Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study. Lung Cancer. 155:20–27. 2021. View Article : Google Scholar : PubMed/NCBI

116 

Zhang C, Zhang S, Yao Y, Huang J, Peng K, Gao Q, Chen H, Xu C, Zhang X, Wu Y, Yang J, et al: MA12. 08 Chemotherapy plus EGFR TKIs or bevacizumab versus chemotherapy alone in SCLC-transformed EGFR-mutant lung adenocarcinoma. J Thor Oncol. 16:S178–S179. 2021. View Article : Google Scholar

117 

Kuiper JL, Ronden MI, Becker A, Heideman DA, van Hengel P, Ylstra B, Thunnissen E and Smit EF: Transformation to a squamous cell carcinoma phenotype of an EGFR-mutated NSCLC patient after treatment with an EGFR-tyrosine kinase inhibitor. J Clin Pathol. 68:320–321. 2015. View Article : Google Scholar

118 

Levin PA, Mayer M, Hoskin S, Sailors J, Oliver DH and Gerber DE: Histologic transformation from adenocarcinoma to squamous cell carcinoma as a mechanism of resistance to EGFR inhibition. J Thorac Oncol. 10:e86–e88. 2015. View Article : Google Scholar

119 

Longo L, Mengoli MC, Bertolini F, Bettelli S, Manfredini S and Rossi G: Synchronous occurrence of squamous-cell carcinoma ‘transformation’ and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma. Lung Cancer. 103:24–26. 2017. View Article : Google Scholar : PubMed/NCBI

120 

Roca E, Pozzari M, Vermi W, Tovazzi V, Baggi A, Amoroso V, Nonnis D, Intagliata S and Berruti A: Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case. Lung Cancer. 127:12–18. 2019. View Article : Google Scholar : PubMed/NCBI

121 

Liao J, Li Y, Liu C, Long Q and Wang J: Case report: EGFR-Positive early-stage lung adenocarcinoma transforming to squamous cell carcinoma after TKI treatment. Front Oncol. 11:6968812021. View Article : Google Scholar

122 

Jukna A, Montanari G, Mengoli MC, Cavazza A, Covi M, Barbieri F, Bertolini F and Rossi G: Squamous Cell Carcinoma ‘Transformation’ concurrent with secondary T790M mutation in resistant EGFR-Mutated Adenocarcinomas. J Thorac Oncol. 11:e49–e51. 2016. View Article : Google Scholar

123 

Bugano DDG, Kalhor N, Zhang J, Neskey M and William WN Jr: Squamous-cell transformation in a patient with lung adenocarcinoma receiving erlotinib: Co-occurrence with T790M mutation. Cancer Treat Comm. 4:34–36. 2015. View Article : Google Scholar

124 

Park S, Shim JH, Lee B, Cho I, Park WY, Kim Y, Lee SH, Choi Y, Han J, Ahn JS, et al: Paired genomic analysis of squamous cell carcinoma transformed from EGFR-mutated lung adenocarcinoma. Lung Cancer. 134:7–15. 2019. View Article : Google Scholar : PubMed/NCBI

125 

Weng CH, Chen LY, Lin YC, Shih JY, Lin YC, Tseng RY, Chiu AC, Yeh YH, Liu C, Lin YT, et al: Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common mechanism for acquired resistance to EGFR TKI. Oncogene. 38:455–468. 2019. View Article : Google Scholar : PubMed/NCBI

126 

Brabletz S, Schuhwerk H, Brabletz T and Stemmler MP: Dynamic EMT: A multi-tool for tumor progression. EMBO J. 40:e1086472021. View Article : Google Scholar : PubMed/NCBI

127 

Zhu X, Chen L, Liu L and Niu X: EMT-Mediated Acquired EGFR-TKI resistance in NSCLC: Mechanisms and strategies. Front Oncol. 9:10442019. View Article : Google Scholar

128 

Miralaei N, Majd A, Ghaedi K, Peymani M and Safaei M: Integrated pan-cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance. Cancer Med. 10:6428–6441. 2021. View Article : Google Scholar : PubMed/NCBI

129 

Nilsson MB, Sun H, Robichaux J, Pfeifer M, McDermott U, Travers J, Diao L, Xi Y, Tong P, Shen L, et al: A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components. Sci Transl Med. 12:eaaz45892020. View Article : Google Scholar : PubMed/NCBI

130 

Wang CY, Lee MH, Kao YR, Hsiao SH, Hong SY and Wu CW: Alisertib inhibits migration and invasion of EGFR-TKI resistant cells by partially reversing the epithelial-mesenchymal transition. Biochim Biophys Acta Mol Cell Res. 1868:1190162021. View Article : Google Scholar : PubMed/NCBI

131 

Yeh CT, Chen TT, Satriyo PB, Wang CH, Wu ATH, Chao TY, Lee KY, Hsiao M, Wang LS and Kuo KT: Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma. Oncogenesis. 10:562021. View Article : Google Scholar : PubMed/NCBI

132 

Liao BC, Griesing S and Yang JC: Second-line treatment of EGFR T790M-negative non-small cell lung cancer patients. Ther Adv Med Oncol. Nov 25–2019.(Epub ahead of print). View Article : Google Scholar

133 

Lee CK, Man J, Lord S, Links M, Gebski V, Mok T and Yang JC: Checkpoint Inhibitors in Metastatic EGFR-Mutated non-small cell lung cancer-A meta-analysis. J Thorac Oncol. 12:403–407. 2017. View Article : Google Scholar

134 

Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T and Yang JC: Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: A systematic review and meta-analysis. JAMA Oncol. 4:210–216. 2018. View Article : Google Scholar

135 

Yang CY, Liao WY, Ho CC, Chen KY, Tsai TH, Hsu CL, Su KY, Chang YL, Wu CT, Hsu CC, et al: Association between programmed death-ligand 1 expression, immune microenvironments, and clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients treated with tyrosine kinase inhibitors. Eur J Cancer. 124:110–122. 2020. View Article : Google Scholar : PubMed/NCBI

136 

Isomoto K, Haratani K, Hayashi H, Shimizu S, Tomida S, Niwa T, Yokoyama T, Fukuda Y, Chiba Y, Kato R, et al: Impact of EGFR-TKI treatment on the tumor immune microenvironment in EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res. 26:2037–2046. 2020. View Article : Google Scholar : PubMed/NCBI

137 

Reck M, Mok TS, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, et al: Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 7:387–401. 2019. View Article : Google Scholar : PubMed/NCBI

138 

Wu SG, Ho CC, Yang JC, Lia BC, Yang CY, Lin YT, Yu CJ, Liao WY and Shih JY: 12P A phase II study of atezolizumab in combination with bevacizumab, carboplatin or cisplatin, and pemetrexed for EGFR-mutant metastatic NSCLC patients after failure of EGFR TKIs. Ann Oncol. 33:S33–S34. 2022. View Article : Google Scholar

139 

Lam TC, Tsang KC, Choi HC, Lee VH, Lam KO, Chiang CL, So TH, Chan WW, Nyaw SF, Lim F, et al: Combination atezolizumab, bevacizumab, pemetrexed and carboplatin for metastatic EGFR mutated NSCLC after TKI failure. Lung Cancer. 159:18–26. 2021. View Article : Google Scholar : PubMed/NCBI

140 

Ren S, Zhang J, Zhao Y, Zhou J, Fan Y, Shu Y, Liu X, Zhang H, He J, Gao G, et al: A multi-center phase II study of toripalimab with chemotherapy in patients with EGFR mutant advanced NSCLC patients resistant to EGFR TKIs: Efficacy and biomarker analysis. Am Soc Clin Oncol. 6:3552020.

141 

Jiang T, Wang P, Zhang J, Zhao Y, Zhou J, Fan Y, Shu Y, Liu X, Zhang H, He J, et al: Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: A multicenter phase-II trial. Signal Transduct Target Ther. 6:3552021. View Article : Google Scholar : PubMed/NCBI

142 

Lu S, Wu L, Jian H, Cheng Y, Wang Q, Fang J, Wang Z, Hu Y, Sun M, Han L, et al: VP9-2021: ORIENT-31: Phase III study of sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy. Ann Oncol. 33:112–113. 2022. View Article : Google Scholar

143 

Hayashi H, Sugawara S, Fukuda Y, Fujimoto D, Miura S, Ota K, Ozawa Y, Hara S, Tanizaki J, Azuma K, et al: A randomized phase II study comparing nivolumab with carboplatin-pemetrexed for EGFR-mutated NSCLC with resistance to EGFR tyrosine kinase inhibitors (WJOG8515L). Clin Cancer Res. 28:893–902. 2022. View Article : Google Scholar : PubMed/NCBI

144 

de Rouw N, Piet B, Derijks HJ, van den Heuvel MM and Ter Heine R: Mechanisms, management and prevention of pemetrexed-related toxicity. Drug Saf. 44:1271–1281. 2021. View Article : Google Scholar : PubMed/NCBI

145 

Liang SK, Keng LT, Chang CH, Wen YF, Lee MR, Yang CY, Wang JY, Ko JC, Shih JY and Yu CJ: Treatment options of first-line tyrosine kinase inhibitors and subsequent systemic chemotherapy agents for advanced EGFR mutant lung adenocarcinoma patients: Implications from Taiwan cancer registry cohort. Front Oncol. 10:5903562021. View Article : Google Scholar

146 

Li Z, Guo H, Lu Y, Hu J, Luo H and Gu W: Chemotherapy with or without pemetrexed as second-line regimens for advanced non-small-cell lung cancer patients who have progressed after first-line EGFR TKIs: A systematic review and meta-analysis. Onco Targets Ther. 11:3697–3703. 2018. View Article : Google Scholar : PubMed/NCBI

147 

Yoo KH, Lee SJ, Cho J, Lee KH, Park KU, Kim KH, Cho EK, Choi YH, Kim HR, Kim HG, et al: A randomized, open-label, Phase II study comparing pemetrexed plus cisplatin followed by maintenance pemetrexed versus pemetrexed alone in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer after failure of first-line EGFR tyrosine kinase inhibitor: KCSG-LU12-13. Cancer Res Treat. 51:718–726. 2019. View Article : Google Scholar

148 

Le X, Nilsson M, Goldman J, Reck M, Nakagawa K, Kato T, Ares LP, Frimodt-Moller B, Wolff K, Visseren-Grul C, et al: Dual EGFR-VEGF Pathway inhibition: A promising strategy for patients with EGFR-Mutant NSCLC. J Thorac Oncol. 16:205–215. 2021. View Article : Google Scholar

149 

Lian Z, Du W, Zhang Y, Fu Y, Liu T, Wang A, Cai T, Zhu J, Zeng Y, Liu Z and Huang JA: Anlotinib can overcome acquired resistance to EGFR-TKIs via FGFR1 signaling in non-small cell lung cancer without harboring EGFR T790M mutation. Thorac Cancer. 11:1934–1943. 2020. View Article : Google Scholar : PubMed/NCBI

150 

Zhang C, Cao H, Cui Y, Jin S, Gao W, Huang C and Guo R: Concurrent use of anlotinib overcomes acquired resistance to EGFR-TKI in patients with advanced EGFR-mutant non-small cell lung cancer. Thorac Cancer. 12:2574–2584. 2021. View Article : Google Scholar : PubMed/NCBI

151 

Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, et al: Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study). Cancer. 124:3830–3838. 2018. View Article : Google Scholar : PubMed/NCBI

152 

Yang R, Wang D, Li X, Mao K, Wang J, Li P, Shi X, Zhang S and Wang Y: An advanced non-small cell lung cancer patient with EGFR and KRAS mutations, and PD-L1 positive, benefited from immunotherapy: A case report. Ann Transl Med. 10:3812022. View Article : Google Scholar : PubMed/NCBI

153 

Bai M, Wang W, Gao X, Wu L, Jin P, Wu H, Yu J and Meng X: Efficacy of immune checkpoint inhibitors in patients with EGFR Mutated NSCLC and potential risk factors associated with prognosis: A single institution experience. Front Immunol. 13:8324192022. View Article : Google Scholar

154 

Mu Y, Hao X, Xing P, Hu X, Wang Y, Li T, Zhang J, Xu Z and Li J: Acquired resistance to osimertinib in patients with non-small-cell lung cancer: Mechanisms and clinical outcomes. J Cancer Res Clin Oncol. 146:2427–2433. 2020. View Article : Google Scholar

155 

Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E and Tiseo M: Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 121:725–737. 2019. View Article : Google Scholar : PubMed/NCBI

156 

He J, Huang Z, Han L, Gong Y and Xie C: Mechanisms and management of 3rd-generation EGFR-TKI resistance in advanced non-small cell lung cancer (Review). Int J Oncol. 59:902021. View Article : Google Scholar

157 

Papadimitrakopoulou V, Wu YL, Han JY, Ahn MJ, Ramalingam SS, John T, Okamoto I, Yang JC, Bulusu K, Laus G, et al: Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study. Annal Oncol. 29:viii7412018. View Article : Google Scholar

158 

Piotrowska Z, Nagy R, Fairclough S, Lanman R, Marcoux N, Gettinger S, Owonikoko T, Ramalingam S and Sequist L: Characterizing the genomic landscape of EGFR C797S in lung cancer using ctDNA next-generation sequencing. J Thorac Oncol. 12:S17672017. View Article : Google Scholar

159 

Wang X, Zhou L, Yin JC, Wu X, Shao YW and Gao B: Lung adenocarcinoma harboring EGFR 19del/C797S/T790M triple mutations responds to brigatinib and Anti-EGFR antibody combination therapy. J Thorac Oncol. 14:e85–e88. 2019. View Article : Google Scholar

160 

Chang Y, Liu S, Jiang Y, Hua L and Wen L: Effective treatment of pulmonary adenocarcinoma harboring triple EGFR mutations of L858R, T790M, cis-G796s/cis-C797s by osimertinib, brigatinib, and bevacizumab combination therapy: A case report. Respir Med Case Rep. 36:1015822022.PubMed/NCBI

161 

Zhou R, Song L, Zhang W, Shao L and Li X and Li X: Combination of osimertinib and anlotinib may overcome the resistance mediated by in cis EGFR T790M-C797S in NSCLC: A case report. Onco Targets Ther. 14:2847–2851. 2021. View Article : Google Scholar : PubMed/NCBI

162 

Yang Y, Xu H, Ma L, Yang L, Yang G, Zhang S, Ai X, Zhang S and Wang Y: Possibility of brigatinib-based therapy, or chemotherapy plus anti-angiogenic treatment after resistance of osimertinib harboring EGFR T790M-cis-C797S mutations in lung adenocarcinoma patients. Cancer Med. 10:8328–8337. 2021. View Article : Google Scholar : PubMed/NCBI

163 

Zhao Y, Chen Y, Huang H, Li X, Shao L and Ding H: Significant benefits of afatinib and apatinib in a refractory advanced NSCLC patient resistant to osimertinib: A case report. OncoTargets Ther. 14:3063–3067. 2021. View Article : Google Scholar

164 

Yang Z, Yang N, Ou Q, Xiang Y, Jiang T, Wu X, Bao H, Tong X, Wang X, Shao YW, et al: Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients. Clin Cancer Res. 24:3097–3107. 2018. View Article : Google Scholar : PubMed/NCBI

165 

Zhang Y, He B, Zhou D, Li M and Hu C: Newly emergent acquired EGFR exon 18 G724S mutation after resistance of a T790M specific EGFR inhibitor osimertinib in non-small-cell lung cancer: A case report. OncoTargets Ther. 12:51–56. 2018. View Article : Google Scholar

166 

Schoenfeld AJ, Chan JM, Kubota D, Sato H, Rizvi H, Daneshbod Y, Chang JC, Paik PK, Offin M, Arcila ME, et al: Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in EGFR-Mutant lung cancer. Clin Cancer Res. 26:2654–2663. 2020. View Article : Google Scholar : PubMed/NCBI

167 

Fairclough SR, Kiedrowski LA, Lin JJ, Zelichov O, Tarcic G, Stinchcombe TE, Odegaard JI, Lanman RB, Shaw AT and Nagy RJ: Identification of osimertinib-resistant EGFR L792 mutations by cfDNA sequencing: oncogenic activity assessment and prevalence in large cfDNA cohort. Exp Hematol Oncol. 8:242019. View Article : Google Scholar

168 

Ma L, Chen R, Wang F, Ma LL, Yuan MM, Chen RR and Liu J: EGFR L718Q mutation occurs without T790M mutation in a lung adenocarcinoma patient with acquired resistance to osimertinib. Ann Transl Med. 7:2072019. View Article : Google Scholar : PubMed/NCBI

169 

Fang W, Huang Y, Gan J, Zheng Q and Zhang L: Emergence of EGFR G724S after progression on osimertinib responded to afatinib monotherapy. J Thorac Oncol. 15:e36–e37. 2020. View Article : Google Scholar

170 

Zhang Y, Yang Q, Zeng X, Wang M, Dong S, Yang B, Tu X, Wei T, Xie W, Zhang C, et al: MET amplification attenuates lung tumor response to immunotherapy by inhibiting STING. Cancer Discov. 11:2726–2737. 2021. View Article : Google Scholar : PubMed/NCBI

171 

Syed YY: Amivantamab: First approval. Drugs. 81:1349–1353. 2021. View Article : Google Scholar : PubMed/NCBI

172 

Amivantamab OK'd for EGFR-Mutant NSCLC, . Cancer Discov. 11:16042021. View Article : Google Scholar

173 

Neijssen J, Cardoso RM, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren PW, Strohl WR and Chiu ML: Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem. 296:1006412021. View Article : Google Scholar : PubMed/NCBI

174 

Planchard D, Loriot Y, André F, Gobert A, Auger N, Lacroix L and Soria JC: EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients. Ann Oncol. 26:2073–2078. 2015. View Article : Google Scholar

175 

Ramalingam S, Cheng Y, Zhou C, Ohe Y, Imamura F, Cho BC, Lin M, Majem M, Shah R, Rukazenkov Y, et al: Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. OncologyPro. 29:viii7402018.

176 

Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, et al: Assessment of resistance mechanisms and clinical implications in patients With EGFR T790M-Positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. 4:1527–1534. 2018. View Article : Google Scholar

177 

Qu F, Zhou Y and Yu WJA-CD: A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance. Anticancer Drugs. 33:e76–e83. 2022. View Article : Google Scholar : PubMed/NCBI

178 

Beenken A and Mohammadi M: The FGF family: Biology, pathophysiology and therapy. Nat Rev Drug Discov. 8:235–253. 2009. View Article : Google Scholar : PubMed/NCBI

179 

Lu Y, Liu Y, Oeck S, Zhang GJ, Schramm A and Glazer PM: Hypoxia induces resistance to EGFR inhibitors in lung cancer cells via upregulation of FGFR1 and the MAPK pathway. Cancer Res. 80:4655–4667. 2020. View Article : Google Scholar : PubMed/NCBI

180 

Quintanal-Villalonga A, Molina-Pinelo S, Cirauqui C, Ojeda-Márquez L, Marrugal Á, Suarez R, Conde E, Ponce-Aix S, Enguita AB, Carnero A, et al: FGFR1 Cooperates with EGFR in lung cancer oncogenesis, and their combined inhibition shows improved efficacy. J Thorac Oncol. 14:641–655. 2019. View Article : Google Scholar

181 

Hayakawa D, Takahashi F, Mitsuishi Y, Tajima K, Hidayat M, Winardi W, Ihara H, Kanamori K, Matsumoto N, Asao T, et al: Activation of insulin-like growth factor-1 receptor confers acquired resistance to osimertinib in non-small cell lung cancer with EGFR T790M mutation. Thorac Cancer. 11:140–149. 2020. View Article : Google Scholar : PubMed/NCBI

182 

Zhao Y, Wang H and He C: Drug resistance of targeted therapy for advanced non-small cell lung cancer harbored EGFR mutation: From mechanism analysis to clinical strategy. J Cancer Res Clin Oncol. 147:3653–3664. 2021. View Article : Google Scholar

183 

Makimoto G, Ninomiya K, Kubo T, Sunami R, Kato Y, Ichihara E, Ohashi K, Rai K, Hotta K, Tabata M, et al: A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant EGFR and activated IGF1R. Jpn J Clin Oncol. 51:956–965. 2021. View Article : Google Scholar

184 

Wang R, Yamada T, Kita K, Taniguchi H, Arai S, Fukuda K, Terashima M, Ishimura A, Nishiyama A, Tanimoto A, et al: Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer. Nat Commun. 11:46072020. View Article : Google Scholar : PubMed/NCBI

185 

Lin CC, Shih JY, Yu CJ, Ho CC, Liao WY, Lee JH, Tsai TH, Su KY, Hsieh MS, Chang YL, et al: Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: A genomic study. Lancet Respir Med. 6:107–116. 2018. View Article : Google Scholar : PubMed/NCBI

186 

Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T, Zhang H, et al: Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 534:129–132. 2016. View Article : Google Scholar : PubMed/NCBI

187 

To C, Jang J, Chen T, Park E, Mushajiang M, De Clercq DJH, Xu M, Wang S, Cameron MD, Heppner DE, et al: Single and dual targeting of mutant EGFR with an allosteric inhibitor. Cancer Discov. 9:926–943. 2019. View Article : Google Scholar : PubMed/NCBI

188 

Tripathi SK and Biswal BK: Allosteric mutant-selective fourth-generation EGFR inhibitors as an efficient combination therapeutic in the treatment of non-small cell lung carcinoma. Drug Discov Today. 26:1466–1472. 2021. View Article : Google Scholar : PubMed/NCBI

189 

Kashima K, Kawauchi H, Tanimura H, Tachibana Y, Chiba T, Torizawa T and Sakamoto H: CH7233163 overcomes osimertinib-resistant EGFR-Del19/T790M/C797S Mutation. Mol Cancer Ther. 19:2288–2297. 2020. View Article : Google Scholar : PubMed/NCBI

190 

Schalm S, Dineen T, Lim S, Park CW, Hsieh J, Woessner R, Zhang Z, Wilson K, Eno M, Wilson D, et al: 1296P BLU-945, a highly potent and selective 4th generation EGFR TKI for the treatment of EGFR T790M/C797S resistant NSCLC. Ann Oncol. 31:S8392020. View Article : Google Scholar

191 

Conti C, Campbell J, Woessner R, Guo J, Timsit Y, Iliou M, Wardwell S, Davis A, Chicklas S, Hsieh J, et al: BLU-701 is a highly potent, brain-penetrant and WT-sparing next-generation EGFR TKI for the treatment of sensitizing (ex19del, L858R) and C797S resistance mutations in metastatic NSCLC. Cancer Res. 81 (Suppl 13):12622021. View Article : Google Scholar

192 

Lim SM, Park CW, Zhang Z, Woessner R, Dineen T, Stevison F, Hsieh J, Eno M, Wilson D, Campbell J, et al: BLU-945, a fourth-generation, potent and highly selective epidermal growth factor receptor tyrosine kinase inhibitor with intracranial activity, demonstrates robust in vivo anti-tumor activity in models of osimertinib-resistant non-small cell lung cancer. Cancer Res. 81 (Suppl 13):14672021. View Article : Google Scholar

193 

Tavera L, Zhang Z, Wardwell S, Job E, McGinn K, Chen M, Iliou M, Albayya F, Campbell J, Eno M, et al: BLU-701 tumour suppression and intracranial activity as a single agent and in combination with BLU-945 in models of non-small cell lung cancer (NSCLC) driven by EGFR mutations. Mol Cell Biol. 165:S372022.

194 

Liu X, Zhang X, Yang L, Chen S, Tian X, Dong T, Ding CZ, Hu L, Wu L, Zhao L, Mao J, et al: Preclinical evaluation of TQB3804, a potent EGFR C797S inhibitor. Cancer Res. 79 (Suppl 13):13202019. View Article : Google Scholar

195 

Huang J and Wang H: Targeted therapy and mechanism of drug resistance in non-small cell lung cancer with epidermal growth factor receptor gene mutation. Zhongguo Fei Ai Za Zhi. 25:183–192. 2022.(In Chinese).

196 

Lim S, Kim DW, Jung JE, Lee G, Ryou JH, Kang SU, Lee YH, Shin HJ, Yum SY and Yim Ε: A Phase 1/2, open-label study of BBT-176, a triple mutation targeting EGFR TKI, in patients with NSCLC who progressed after prior EGFR TKI therapy. Ann Oncol. 32:S949–S1039. 2021. View Article : Google Scholar

197 

Lim S, Kim D and Jung J: A phase I/II, open-label study of BBT-176, a triple mutation targeting EGFR TKI, in patients with NSCLC who progressed after prior EGFR TKI therapy. Ann Oncol. 32:S1035(Suppl 5):2021.

198 

Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, et al: Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the CHRYSALIS phase I study. J Clin Oncol. 39:3391–3402. 2021. View Article : Google Scholar

199 

Cho B, Lee K, Cho E, Kim DW, Lee JS, Han JY, Kim SW, Spira A, Haura EB, Sabari JK, et al: 1258O Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in combination with lazertinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in advanced EGFR NSCLC. Ann Oncol. 31:S813(Suppl 4):2020. View Article : Google Scholar

200 

Yu H, Johnson M, Steuer C, Vigliotti M, Chen S, Kamai Y, Yu C and Jänne P: Preliminary phase 1 results of U3-1402-A novel HER3-targeted antibody-drug conjugate-in EGFR TKI-resistant, EGFR-mutant NSCLC. Mol Cell Biol. 14:S336–S337. 2019.

201 

Jänne PA, Baik C, Su WC, Johnson ML, Hayashi H, Nishio M, Kim DW, Koczywas M, Gold KA, Steuer CE, et al: Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated non-small cell lung cancer. Cancer Discov. 12:74–89. 2022. View Article : Google Scholar

202 

Soo RA, Han JY, Dafni U, Cho BC, Yeo CM, Nadal E, Carcereny E, de Castro J, Sala MA, Bernabé R, et al: A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: The European Thoracic Oncology Platform (ETOP 10–16) BOOSTER trial. Ann Oncol. 33:181–192. 2022. View Article : Google Scholar

203 

Cui Q, Hu Y, Cui Q, Wu D, Mao Y, Ma D and Liu H: Osimertinib rechallenge with bevacizumab vs. chemotherapy plus bevacizumab in EGFR-Mutant NSCLC patients with osimertinib resistance. Front Pharmacol. 12:7467072022. View Article : Google Scholar

204 

Sequist L, Peled N, Tufman A, Servidio L, Li J, Taylor R and Zhao J: COMPEL: Chemotherapy with/without osimertinib in patients with EGFRm advanced NSCLC and progression on first-line osimertinib. J Thor Oncol. 16:S11012021. View Article : Google Scholar

205 

Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, et al: Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: The ALTER 0303 phase 3 Randomized clinical trial. JAMA Oncol. 4:1569–1575. 2018. View Article : Google Scholar

206 

Tamiya M, Kunimasa K, Nishino K, Matsumoto S, Kawachi H, Kuno K, Inoue T, Kuhara H, Imamura F, Goto K and Kumagai T: Successful treatment of an osimertinib-resistant lung adenocarcinoma with an exon 18 EGFR mutation (G719S) with afatinib plus bevacizumab. Invest New Drugs. 39:232–236. 2021. View Article : Google Scholar : PubMed/NCBI

207 

Blakely CM, Watkins TBK, Wu W, Gini B, Chabon JJ, McCoach CE, McGranahan N, Wilson GA, Birkbak NJ, Olivas VR, et al: Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet. 49:1693–1704. 2017. View Article : Google Scholar

208 

Dagogo-Jack I and Shaw AT: Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 15:81–94. 2018. View Article : Google Scholar

209 

Assaraf YG, Brozovic A, Gonçalves AC, Jurkovicova D, Linē A, Machuqueiro M, Saponara S, Sarmento-Ribeiro AB, Xavier CPR and Vasconcelos MH: The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resist Updat. 46:1006452019. View Article : Google Scholar

210 

Zhang Y, Wang D, Peng M, Tang L, Ouyang J, Xiong F, Guo C, Tang Y, Zhou Y, Liao Q, et al: Single-cell RNA sequencing in cancer research. J Exp Clin Cancer Res. 40:812021. View Article : Google Scholar : PubMed/NCBI

211 

Maynard A, McCoach CE, Rotow JK, Harris L, Haderk F, Kerr DL, Yu EA, Schenk EL, Tan W, Zee A, et al: Therapy-Induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell. 182:1232–1251.e22. 2020. View Article : Google Scholar

212 

Kim DW and Cho JY: Recent advances in allogeneic CAR-T cells. Biomolecules. 10:2632020. View Article : Google Scholar

213 

Patel AJ, Richter A, Drayson MT and Middleton GW: The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer. Cancer Immunol Immunother. 69:325–342. 2020. View Article : Google Scholar : PubMed/NCBI

214 

Hung LVM, Ngo HT and Van Pham P: Clinical trials with cytokine-induced killer cells and CAR-T cell transplantation for non-small cell lung cancer treatment. Adv Exp Med Biol. 1292:113–130. 2020. View Article : Google Scholar

215 

Johnson LA and June CH: Driving gene-engineered T cell immunotherapy of cancer. Cell Res. 27:38–58. 2017. View Article : Google Scholar : PubMed/NCBI

216 

Xu J, Zhang Q, Tian K, Wang H, Yin H and Zheng J: Current status and future prospects of the strategy of combining CAR-T with PD-1 blockade for antitumor therapy (Review). Mol Med Rep. 17:2083–2088. 2018.PubMed/NCBI

217 

Kandra P, Nandigama R, Eul B, Huber M, Kobold S, Seeger W, Grimminger F and Savai R: Utility and drawbacks of chimeric antigen receptor T Cell (CAR-T) therapy in lung cancer. Front Immunol. 13:9035622022. View Article : Google Scholar

218 

Xu C, Ju D and Zhang X: Chimeric antigen receptor T-cell therapy: Challenges and opportunities in lung cancer. Antib Ther. 5:73–83. 2022.PubMed/NCBI

219 

Yang P, Qiao Y, Meng M and Zhou Q: Cancer/Testis antigens as biomarker and target for the diagnosis, prognosis, and therapy of lung cancer. Front Oncol. 12:8641592022. View Article : Google Scholar

220 

Yeku O, Li X and Brentjens RJ: Adoptive T-Cell therapy for solid tumors. Am Soc Clin Oncol Educ Book. 37:193–204. 2017. View Article : Google Scholar : PubMed/NCBI

221 

Reppel L, Tsahouridis O, Akulian J, Davis IJ, Lee H, Fucà G, Weiss J, Dotti G, Pecot CV and Savoldo B: Targeting disialoganglioside GD2 with chimeric antigen receptor-redirected T cells in lung cancer. J Immunother Cancer. 10:e0038972022. View Article : Google Scholar : PubMed/NCBI

222 

Min J, Long C, Zhang L, Duan J, Fan H, Chu F and Li Z: c-Met specific CAR-T cells as a targeted therapy for non-small cell lung cancer cell A549. Bioengineered. 13:9216–9232. 2022. View Article : Google Scholar : PubMed/NCBI

223 

Feng K, Guo Y, Dai H, Wang Y, Li X, Jia H and Han W: Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci. 59:468–479. 2016. View Article : Google Scholar

224 

Xiao BF, Zhang JT, Zhu YG, Cui XR, Lu ZM, Yu BT and Wu N: Chimeric antigen receptor T-Cell therapy in lung cancer: Potential and challenges. Front Immunol. 12:7827752021. View Article : Google Scholar

225 

Qu J, Mei Q, Chen L and Zhou J: Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): Current status and future Aperspectives. Cancer Immunol Immunother. 70:619–631. 2021. View Article : Google Scholar : PubMed/NCBI

226 

Chen L, Chen F, Li J, Pu Y, Yang C, Wang Y, Lei Y and Huang Y: CAR-T cell therapy for lung cancer: Potential and perspective. Thorac Cancer. 13:889–899. 2022. View Article : Google Scholar : PubMed/NCBI

227 

Vasic D, Lee JB, Leung Y, Khatri I, Na Y, Abate-Daga D and Zhang L: Allogeneic double-negative CAR-T cells inhibit tumor growth without off-tumor toxicities. Sci Immunol. 7:eabl36422022. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sun R, Hou Z, Zhang Y and Jiang B: Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review). Oncol Lett 24: 408, 2022.
APA
Sun, R., Hou, Z., Zhang, Y., & Jiang, B. (2022). Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review). Oncology Letters, 24, 408. https://doi.org/10.3892/ol.2022.13528
MLA
Sun, R., Hou, Z., Zhang, Y., Jiang, B."Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)". Oncology Letters 24.5 (2022): 408.
Chicago
Sun, R., Hou, Z., Zhang, Y., Jiang, B."Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)". Oncology Letters 24, no. 5 (2022): 408. https://doi.org/10.3892/ol.2022.13528
Copy and paste a formatted citation
x
Spandidos Publications style
Sun R, Hou Z, Zhang Y and Jiang B: Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review). Oncol Lett 24: 408, 2022.
APA
Sun, R., Hou, Z., Zhang, Y., & Jiang, B. (2022). Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review). Oncology Letters, 24, 408. https://doi.org/10.3892/ol.2022.13528
MLA
Sun, R., Hou, Z., Zhang, Y., Jiang, B."Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)". Oncology Letters 24.5 (2022): 408.
Chicago
Sun, R., Hou, Z., Zhang, Y., Jiang, B."Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)". Oncology Letters 24, no. 5 (2022): 408. https://doi.org/10.3892/ol.2022.13528
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team