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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
March-2026 Volume 55 Issue 3

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
March-2026 Volume 55 Issue 3

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

Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)

  • Authors:
    • Upesh Sharma
    • Jincheng Song
    • Hemraj Kandu
    • Yue Zhu
    • Zhaoxia Dai
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China
    Copyright: © Sharma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 39
    |
    Published online on: January 8, 2026
       https://doi.org/10.3892/or.2026.9044
  • 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

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most frequent oncogenic drivers in cancer, particularly in non‑small cell lung cancer (NSCLC). KRAS was previously considered an ‘undruggable’ target due to the protein's smooth molecular surface and the absence of obvious drug binding sites. However, the development of selective KRAS G12C inhibitors, such as sotorasib and adagrasib, together with progress in immunotherapy, have demonstrated potential clinical activity. Further understanding of the complex signaling networks driven by KRAS has revealed new opportunities to target this pathway directly or through rational combination strategies. The present review explored KRAS‑targeted therapies and immunotherapies, including limitations, resistance mechanisms and the efficacy of combination regimens. Although there has been notable progress, concerns regarding optimal therapy combinations, resistance management and early treatment strategies remain. The present review demonstrated the need for continued research to address these challenges and improve outcomes for patients with KRAS‑mutated NSCLC.
View Figures

Figure 1

(A) Normal KRAS signaling. KRAS
exists in a normal balance between its inactive form bound to GDP
and the active form bound to GTP. It balances the activation of
several downstream pathways, including RAF/MEK/ERK, RAL/RLIP and
PI3K/AKT/mTOR, which execute regulated cellular features such as
proliferation, migration, survival and differentiation. (B)
Oncogenic KRAS signaling. Mutations disrupt the normal function of
GTPase-activating proteins that hydrolyze GTP to GDP, resulting in
constitutively active KRAS. Constitutive activation thus propagates
a sustained drive for downstream signaling that promotes cell
proliferation, migration, survival and differentiation, which are
associated with oncogenic signaling. KRAS, Kirsten rat sarcoma
viral oncogene homolog; GAP, GTPase activating proteins; GEF,
guanine nucleotide exchange factors; RLIP, RalA binding protein
1.
View References

1 

El Osta B, Behera M, Kim S, Berry LD, Sica G, Pillai RN, Owonikoko TK, Kris MG, Johnson BE, Kwiatkowski DJ, et al: Characteristics and outcomes of patients with metastatic KRAS-mutant lung adenocarcinomas: The lung cancer mutation consortium experience. J Thorac Oncol. 14:876–889. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Moore AR, Rosenberg SC, McCormick F and Malek S: RAS-targeted therapies: is the undruggable drugged? Nat Rev Drug Discov. 19:533–552. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Simanshu DK, Nissley DV and McCormick F: RAS proteins and their regulators in human disease. Cell. 170:17–33. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Prior IA, Hood FE and Hartley JL: The frequency of ras mutations in cancer. Cancer Res. 80:2669–2974. 2020. View Article : Google Scholar : PubMed/NCBI

5 

Dearden S, Stevens J, Wu YL and Blowers D: Mutation incidence and coincidence in non small-cell lung cancer: Meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 24:2371–2376. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Yang H, Liang SQ, Schmid RA and Peng RW: New horizons in KRAS-mutant lung cancer: Dawn after darkness. Front Oncol. 9:9532019. View Article : Google Scholar : PubMed/NCBI

7 

Naim MJ, Alam MJ, Ahmad S, Nawaz F, Shrivastava N, Sahu M and Alam O: Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: An insight into structure activity relationship. Eur J Med Chem. 129:218–250. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Bos JL: Ras oncogenes in human cancer: A review. Cancer Res. 49:4682–4689. 1989.PubMed/NCBI

9 

Prior IA, Lewis PD and Mattos C: A comprehensive survey of Ras mutations in cancer. Cancer Res. 72:2457–2467. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Yin G, Huang J, Petela J, Jiang H, Zhang Y, Gong S, Wu J, Liu B, Shi J and Gao Y: Targeting small GTPases: Emerging grasps on previously untamable targets, pioneered by KRAS. Signal Transduct Target Ther. 8:2122023. View Article : Google Scholar : PubMed/NCBI

11 

Michalak DJ, Unger B, Lorimer E, Grishaev A, Williams CL, Heinrich F and Lösche M: Structural and biophysical properties of farnesylated KRas interacting with the chaperone SmgGDS-558. Biophys J. 121:3684–3697. 2022. View Article : Google Scholar : PubMed/NCBI

12 

Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Jeon H, Wang S, Song J, Gill H and Cheng H: Update 2025: Management of non-small-cell lung cancer. Lung. 203:532025. View Article : Google Scholar : PubMed/NCBI

14 

Huang L, Guo Z, Wang F and Fu L: KRAS mutation: From undruggable to druggable in cancer. Signal Transduct Target Ther. 6:3862021. View Article : Google Scholar : PubMed/NCBI

15 

Zhang F, Wang B, Wu M, Zhang L and Ji M: Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: A systematic review. Front Immunol. 16:15091732025. View Article : Google Scholar : PubMed/NCBI

16 

Uniyal P, Kashyap VK, Behl T, Parashar D and Rawat R: KRAS mutations in cancer: Understanding signaling pathways to immune regulation and the potential of immunotherapy. Cancers (Basel). 17:7852025. View Article : Google Scholar : PubMed/NCBI

17 

Parikh K, Banna G, Liu SV, Friedlaender A, Desai A, Subbiah V and Addeo A: Drugging KRAS: Current perspectives and state-of-art review. J Hematol Oncol. 15:1522022. View Article : Google Scholar : PubMed/NCBI

18 

Hamarsheh S, Groß O, Brummer T and Zeiser R: Immune modulatory effects of oncogenic KRAS in cancer. Nat Commun. 11:54392020. View Article : Google Scholar : PubMed/NCBI

19 

Ghimessy A, Radeczky P, Laszlo V, Hegedus B, Renyi-Vamos F, Fillinger J, Klepetko W, Lang C, Dome B and Megyesfalvi Z: Current therapy of KRAS-mutant lung cancer. Cancer Metastasis Rev. 39:1159–1177. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Eser M, Hekimoglu G, Yarar MH, Canbek S and Ozcelik M: KRAS G12C mutation in NSCLC in a small genetic center: Insights into sotorasib therapy response potential. Sci Rep. 14:265812024. View Article : Google Scholar : PubMed/NCBI

21 

Bourne HR, Sanders DA and McCormick F: The GTPase superfamily: A conserved switch for diverse cell functions. Nature. 348:125–132. 1990. View Article : Google Scholar : PubMed/NCBI

22 

Bourne HR, Sanders DA and McCormick F: The GTPase superfamily: Conserved structure and molecular mechanism. Nature. 349:117–127. 1991. View Article : Google Scholar : PubMed/NCBI

23 

Scheffzek K, Ahmadian MR, Kabsch W, Wiesmüller L, Lautwein A, Schmitz F and Wittinghofer A: The Ras-RasGAP complex: Structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 277:333–338. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Martin P, Leighl NB, Tsao MS and Shepherd FA: KRAS mutations as prognostic and predictive markers in non-small cell lung cancer. J Thorac Oncol. 8:530–542. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Adderley H, Blackhall FH and Lindsay CR: KRAS-mutant non-small cell lung cancer: Converging small molecules and immune checkpoint inhibition. EBioMedicine. 41:711–716. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Matikas A, Mistriotis D, Georgoulias V and Kotsakis A: Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity. Crit Rev Oncol Hematol. 110:1–12. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Shepherd FA, Domerg C, Hainaut P, Jänne PA, Pignon JP, Graziano S, Douillard JY, Brambilla E, Le Chevalier T, Seymour L, et al: Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol. 31:2173–2181. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Riely GJ, Kris MG, Rosenbaum D, Marks J, Li A, Chitale DA, Nafa K, Riedel ER, Hsu M, Pao W, et al: Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 14:5731–5734. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Redig AJ, Chambers ES, Lydon CA, Dahlberg SE, Alden RS and Janne PA: Genomic complexity in KRAS mutant non-small cell lung cancer (NSCLC) from never/light-smokers v smokers. J Clin Oncol. 34 (15 Suppl):S90872016. View Article : Google Scholar

30 

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L and Schmid-Bindert G: KRAS-mutant non-small cell lung cancer: From biology to therapy. Lung Cancer. 124:53–64. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Li S, Liu S, Deng J, Akbay EA, Hai J, Ambrogio C, Zhang L, Zhou F, Jenkins RW, Adeegbe DO, et al: Assessing therapeutic efficacy of MEK inhibition in a KRASG12C-driven mouse model of lung cancer. Clin Cancer Res. 24:4854–4864. 2018. View Article : Google Scholar : PubMed/NCBI

32 

Garassino MC, Marabese M, Rusconi P, Rulli E, Martelli O, Farina G, Scanni A and Broggini M: Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann Oncol. 22:235–237. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, et al: Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 150:1107–1120. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Lee B, Lee T, Lee SH, Choi YL and Han J: Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers. Oncotarget. 7:23874–23884. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Li S, Li L, Zhu Y, Huang C, Qin Y, Liu H, Ren-Heidenreich L, Shi B, Ren H, Chu X, et al: Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: A comprehensive mutation profiling from 5125 Chinese cohorts. Br J Cancer. 110:2812–2820. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL and Paz-Ares L: Lung cancer: Current therapies and new targeted treatments. Lancet. 389:299–311. 2017. View Article : Google Scholar : PubMed/NCBI

37 

Skoulidis F and Heymach JV: Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 19:495–509. 2019. View Article : Google Scholar : PubMed/NCBI

38 

Christensen JG, Olson P, Briere T, Wiel C and Bergo MO: Targeting Krasg12c-mutant cancer with a mutation-specific inhibitor. J Intern Med. 288:183–191. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Haidar M and Jacquemin P: Past and future strategies to inhibit membrane localization of the KRAS oncogene. Int J Mol Sci. 22:131932021. View Article : Google Scholar : PubMed/NCBI

40 

Tomasini P, Walia P, Labbe C, Jao K and Leighl NB: Targeting the KRAS pathway in non-small cell lung cancer. Oncologist. 21:1450–1460. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Gysin S, Salt M, Young A and McCormick F: Therapeutic strategies for targeting ras proteins. Genes Cancer. 2:359–372. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Spoerner M, Herrmann C, Vetter IR, Kalbitzer HR and Wittinghofer A: Dynamic properties of the Ras switch I region and its importance for binding to effectors. Proc Natl Acad Sci USA. 98:4944–4949. 2001. View Article : Google Scholar : PubMed/NCBI

43 

Buhrman G, O'Connor C, Zerbe B, Kearney BM, Napoleon R, Kovrigina EA, Vajda S, Kozakov D, Kovrigin EL and Mattos C: Analysis of binding site hot spots on the surface of Ras GTPase. J Mol Biol. 413:773–789. 2011. View Article : Google Scholar : PubMed/NCBI

44 

Ostrem JM, Peters U, Sos ML, Wells JA and Shokat KM: K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 503:548–551. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Shima F, Matsumoto S, Yoshikawa Y, Kawamura T, Isa M and Kataoka T: Current status of the development of Ras inhibitors. J Biochem. 158:91–99. 2015. View Article : Google Scholar : PubMed/NCBI

46 

Berndt N, Hamilton AD and Sebti SM: Targeting protein prenylation for cancer therapy. Nat Rev Cancer. 11:775–791. 2011. View Article : Google Scholar : PubMed/NCBI

47 

Roberts PJ and Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 26:3291–3310. 2007. View Article : Google Scholar : PubMed/NCBI

48 

Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI and Waldmann H: Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling. Nature. 497:638–642. 2013. View Article : Google Scholar : PubMed/NCBI

49 

Riely GJ, Johnson ML, Medina C, Rizvi NA, Miller VA, Kris MG, Pietanza MC, Azzoli CG, Krug LM, Pao W and Ginsberg MS: A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations. J Thorac Oncol. 6:1435–1437. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Whyte DB, Kirschmeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ, Bishop WR and Pai JK: K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem. 272:14459–14464. 1997. View Article : Google Scholar : PubMed/NCBI

51 

Shima F, Yoshikawa Y, Ye M, Araki M, Matsumoto S, Liao J, Hu L, Sugimoto T, Ijiri Y, Takeda A, et al: In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proc Natl Acad Sci USA. 110:8182–8187. 2013. View Article : Google Scholar : PubMed/NCBI

52 

Gerber DE, Camidge DR, Morgensztern D, Cetnar J, Kelly RJ, Ramalingam SS, Spigel DR, Jeong W, Scaglioni PP, Zhang S, et al: Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer. Lung Cancer. 139:60–67. 2020. View Article : Google Scholar : PubMed/NCBI

53 

Cox AD, Fesik SW, Kimmelman AC, Luo J and Der CJ: Drugging the undruggable RAS: Mission possible? Nat Rev Drug Discov. 13:828–851. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Wang M and Casey PJ: Protein prenylation: Unique fats make their mark on biology. Nat Rev Mol Cell Biol. 17:110–122. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Kazi A, Xiang S, Yang H, Chen L, Kennedy P, Ayaz M, Fletcher S, Cummings C, Lawrence HR, Beato F, et al: Dual farnesyl and geranylgeranyl transferase inhibitor thwarts mutant KRAS-driven patient-derived pancreatic tumors. Clin Cancer Res. 25:5984–5996. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Tao MH, Chen S, Freudenheim JL, Cauley JA, Johnson KC, Mai X, Sarto GE, Wakelee H, Boffetta P and Wactawski-Wende J: Oral bisphosphonate use and lung cancer incidence among postmenopausal women. Ann Oncol. 29:1476–1485. 2018. View Article : Google Scholar : PubMed/NCBI

57 

Nagao S, Hattori N, Fujitaka K, Iwamoto H, Ohshimo S, Kanehara M, Ishikawa N, Haruta Y, Murai H and Kohno N: Regression of a primary pulmonary adenocarcinoma after zoledronic acid monotherapy. Hiroshima J Med Sci. 60:7–9. 2011.PubMed/NCBI

58 

Kitai H, Ebi H, Tomida S, Floros KV, Kotani H, Adachi Y, Oizumi S, Nishimura M, Faber AC and Yano S: Epithelial-to-mesenchymal transition defines feedback activation of receptor tyrosine kinase signaling induced by MEK inhibition in KRAS-mutant lung cancer. Cancer Discov. 6:754–769. 2016. View Article : Google Scholar : PubMed/NCBI

59 

Johnson C, Burkhart DL and Haigis KM: Classification of KRAS-activating mutations and the implications for therapeutic intervention. Cancer Discov. 12:913–923. 2022. View Article : Google Scholar : PubMed/NCBI

60 

Hunter JC, Manandhar A, Carrasco MA, Gurbani D, Gondi S and Westover KD: Biochemical and structural analysis of common cancer-associated KRAS mutations. Mol Cancer Res. 13:1325–1335. 2015. View Article : Google Scholar : PubMed/NCBI

61 

Ostrem JML and Shokat KM: Direct small-molecule inhibitors of KRAS: From structural insights to mechanism-based design. Nat Rev Drug Discov. 15:771–785. 2016. View Article : Google Scholar : PubMed/NCBI

62 

Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, et al: The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 575:217–223. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Pandey D, Chauhan SC, Kashyap VK and Roy KK: Structural insights into small-molecule KRAS inhibitors for targeting KRAS mutant cancers. Eur J Med Chem. 277:1167712024. View Article : Google Scholar : PubMed/NCBI

64 

Warnecke B and Nagasaka M: Adagrasib in the treatment of KRAS p.G12C positive advanced NSCLC: Design, development and place in therapy. Drug Des Devel Ther. 18:5673–5683. 2024. View Article : Google Scholar : PubMed/NCBI

65 

Li Z, Song Z, Zhao Y, Wang P, Jiang L, Gong Y, Zhou J, Jian H, Dong X, Zhuang W, et al: D-1553 (Garsorasib), a potent and selective inhibitor of KRASG12C in patients with NSCLC: Phase 1 study results. J Thorac Oncol. 18:940–951. 2023. View Article : Google Scholar : PubMed/NCBI

66 

D'Alessio-Sands L, Gaynier J, Michel-Milian V, Agbowuro AA and Brackett CM: Current strategies and future dimensions in the development of KRAS inhibitors for targeted anticancer therapy. Drug Dev Res. 86:e700422025. View Article : Google Scholar : PubMed/NCBI

67 

Deming DA: Development of KRAS inhibitors and their role for metastatic colorectal cancer. J Natl Compr Canc Netw. 23:e2470672025. View Article : Google Scholar : PubMed/NCBI

68 

Zhao T and Liang SH: Novel tricyclic KRAS inhibitors for the treatment of cancer. ACS Med Chem Lett. 16:178–179. 2025. View Article : Google Scholar : PubMed/NCBI

69 

Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, et al: KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 383:1207–1217. 2020. View Article : Google Scholar : PubMed/NCBI

70 

No authors listed. FDA approves first KRAS inhibitor: Sotorasib. Cancer Discov. 11:OF42021. View Article : Google Scholar

71 

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

72 

Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, et al: Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation. N Engl J Med. 387:120–131. 2022. View Article : Google Scholar : PubMed/NCBI

73 

de Langen AJ, Johnson ML, Mazieres J, Dingemans AC, Mountzios G, Pless M, Wolf J, Schuler M, Lena H, Skoulidis F, et al: Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: A randomised, open-label, phase 3 trial. Lancet. 401:733–746. 2023. View Article : Google Scholar : PubMed/NCBI

74 

Wislez M, Mascaux C, Cadranel J, Thomas QD, Ricordel C, Swalduz A, Pichon E, Veillon R, Gounant V, Rousseau-Bussac G, et al: Real-world effectiveness and tolerability of sotorasib in patients with KRAS G12C-mutated metastatic non-small cell lung cancer: The IFCT-2102 lung KG12Ci study. Eur J Cancer. 219:1153012025. View Article : Google Scholar : PubMed/NCBI

75 

Ou SHI, Jänne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova L, Johnson ML, Velastegui KL, Cilliers C, et al: First-in-human phase I/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRASG12C solid tumors (KRYSTAL-1). J Clin Oncol. 40:2530–2538. 2022. View Article : Google Scholar : PubMed/NCBI

76 

Mok TSK, Yao W, Duruisseaux M, Doucet L, Azkárate Martínez A, Gregorc V, Juan-Vidal O, Lu S, De Bondt C, de Marinis F, et al: KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation. J Clin Oncol. 42 (Suppl 17):LBA85092024. View Article : Google Scholar

77 

Li Z, Dang X, Huang D, Jin S, Li W, Shi J, Wang X, Zhang Y, Song Z, Zhang J, et al: Abstract CT246: Open-label, single-arm, multicenter, phase 2 trial of garsorasib in KRAS G12C-mutated non-small-cell lung cancer. Cancer Res. 84 (7 Suppl):CT2462024. View Article : Google Scholar

78 

Li Z, Dang X, Huang D, Jin S, Li W, Shi J, Wang X, Zhang Y, Song Z, Zhang J, et al: Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: An open-label, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 12:589–598. 2024. View Article : Google Scholar : PubMed/NCBI

79 

Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, et al: Acquired resistance to KRASG12C inhibition in cancer. N Engl J Med. 384:2382–2393. 2021. View Article : Google Scholar : PubMed/NCBI

80 

Cox AD and Der CJ: ‘Undruggable KRAS’: Druggable after all. Genes Dev. 39:132–162. 2025.PubMed/NCBI

81 

Maruyama K, Shimizu Y, Nomura Y, Oh-Hara T, Takahashi Y, Nagayama S, Fujita N and Katayama R: Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization. NPJ Precis Oncol. 9:42025. View Article : Google Scholar : PubMed/NCBI

82 

Mugarza E, van Maldegem F, Boumelha J, Moore C, Rana S, Llorian Sopena M, East P, Ambler R, Anastasiou P, Romero-Clavijo P, et al: Therapeutic KRASG12C inhibition drives effective interferon-mediated antitumor immunity in immunogenic lung cancers. Sci Adv. 8:eabm87802022. View Article : Google Scholar : PubMed/NCBI

83 

Garassino MC, Jänne PA, Barlesi F, Spira AI, Mok TSK, Hochmair M, O'Byrne KJ, Felip E, Kim SW, Cappuzzo F, et al: 1394TiP KRYSTAL-7: A phase III study of first-line adagrasib plus pembrolizumab versus pembrolizumab alone in patients with advanced NSCLC with KRASG12C mutation mutation. Ann Oncol. 35 (Suppl 2):S872–S873. 2024. View Article : Google Scholar

84 

Li BT, Falchook GS, Durm GA, Burns TF, Skoulidis F, Ramalingam SS, Spira A, Bestvina CM, Goldberg SB, Veluswamy R, et al: OA03.06 CodeBreaK 100/101: First report of safety/efficacy of sotorasib in combination with pembrolizumab or atezolizumab in advanced KRAS p.G12C NSCLC. J Thorac Oncol. 17 (Suppl):S10–S11. 2022. View Article : Google Scholar

85 

Ernst SM, Hofman MM, van der Horst TE, Paats MS, Heijboer FWJ, Aerts JGJV, Dumoulin DW, Cornelissen R, von der Thüsen JH, de Bruijn P, et al: Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: A comprehensive clinical and pharmacokinetic analysis. EBioMedicine. 102:1050742024. View Article : Google Scholar : PubMed/NCBI

86 

Chour A, Basse C, Lebossé F, Bonte PE, Girard N and Duruisseaux M: Management of sotorasib-related adverse events and hepatotoxicities following anti-PD-(L)1 therapy: Experience with sotorasib in two French anti-cancer centers and practical guidance proposal. Lung Cancer. 191:1077892024. View Article : Google Scholar : PubMed/NCBI

87 

Zhang J, Johnson M, Barve M, Bazhenova L, McCarthy M, Schwartz R, Horvath-Walsh E, Velastegui K, Qian C and Spira A: Practical guidance for the management of adverse events in patients with KRASG12C-mutated non-small cell lung cancer receiving adagrasib. Oncologist. 28:287–296. 2023. View Article : Google Scholar : PubMed/NCBI

88 

Mina SA, Shanshal M, Leventakos K and Parikh K: Emerging targeted therapies in non-small-cell lung cancer (NSCLC). Cancers (Basel). 17:3532025. View Article : Google Scholar : PubMed/NCBI

89 

Fancelli S, Petroni G, Pillozzi S and Antonuzzo L: Unconventional strategy could be the future: From target to KRAS broad range treatment. Heliyon. 10:e297392024. View Article : Google Scholar : PubMed/NCBI

90 

Masfarre Pinto L, Parreira ASDFM, Castro Unanua N, Rocha P, Morilla Ruiz I, Teijeira Sanchez L, Clave S, Navarro Gorro N, Bach Mora R, Sánchez I, et al: 1408P Differences on immune biomarkers between KRAS G12C and KRAS non-G12C mutated non-small cell lung cancer. Ann Oncol. 34 (Suppl2):S805–S806. 2023. View Article : Google Scholar

91 

Zhou C, Li C, Luo L, Li X, Jia K, He N, Mao S, Wang W, Shao C, Liu X, et al: Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer. Cancer Cell. 42:1286–1300.e8. 2024. View Article : Google Scholar : PubMed/NCBI

92 

Li Y, Zhao J and Li Y: New exploration of KRASG12D inhibitors and the mechanisms of resistance. Exp Hematol Oncol. 14:392025. View Article : Google Scholar : PubMed/NCBI

93 

Arbour KC, Rizvi H, Plodkowski AJ, Hellmann MD, Knezevic A, Heller G, Yu HA, Ladanyi M, Kris MG, Arcila ME, et al: Treatment outcomes and clinical characteristics of patients with KRAS-G12C-mutant non-small cell lung cancer. Clin Cancer Res. 27:2209–2215. 2021. View Article : Google Scholar : PubMed/NCBI

94 

Bironzo P, Cani M, Jacobs F, Napoli VM, Listì A, Passiglia F, Righi L, Di Maio M, Novello S and Scagliotti GV: Real-world retrospective study of KRAS mutations in advanced non-small cell lung cancer in the era of immunotherapy. Cancer. 129:1662–1671. 2023. View Article : Google Scholar : PubMed/NCBI

95 

Rodenhuis S, van de Wetering ML, Mooi WJ, Evers SG, van Zandwijk N and Bos JL: Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med. 317:929–935. 1987. View Article : Google Scholar : PubMed/NCBI

96 

Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA and Kurzrock R: Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 16:2598–2608. 2017. View Article : Google Scholar : PubMed/NCBI

97 

Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, et al: Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: Results from the IMMUNOTARGET registry. Ann Oncol. 30:1321–1328. 2019. View Article : Google Scholar : PubMed/NCBI

98 

Rothschild SI: KRAS and immune checkpoint inhibitors-serendipity raising expectations. J Thorac Oncol. 14:951–954. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Torralvo J, Friedlaender A, Achard V and Addeo A: The activity of immune checkpoint inhibition in KRAS mutated non-small cell lung cancer: A single centre experience. Cancer Genomics Proteomics. 16:577–582. 2019. View Article : Google Scholar : PubMed/NCBI

100 

Mok TSK, Lopes G, Cho BC, Kowalski DM, Kasahara K, Wu YL, de Castro G Jr, Turna HZ, Cristescu R, Aurora-Garg D, et al: Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: Pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC. Ann Oncol. 34:377–388. 2023. View Article : Google Scholar : PubMed/NCBI

101 

Gadgeel S, Rodriguez-Abreu D, Felip E, Esteban E, Speranza G, Reck M, Hui R, Boyer M, Garon EB, Horinouchi H, et al: LBA5-KRAS mutational status and efficacy in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC. Ann Oncol. 30 (Suppl 11):xi64–xi65. 2019. View Article : Google Scholar

102 

Peng L, Guo J, Kong L, Huang Y, Tang N, Zhang J, Wang M, He X, Li Z, Peng Y, et al: Efficacy of immunotherapy in KRAS-mutant advanced NSCLC: A real-world study in a Chinese population. Front Oncol. 12:10707612023. View Article : Google Scholar : PubMed/NCBI

103 

Urtecho SB, Provenzano L, Spagnoletti A, Bottiglieri A, Pircher C, Massa G, Sposetti C, Proto C, Brambilla M, Occhipinti M, et al: Decoding KRAS mutation in non-small cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review. Lung Cancer. 199:1080512025. View Article : Google Scholar : PubMed/NCBI

104 

Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, Buczkowski KA, Liu Y, Awad MM, Denning WL, et al: STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell Activity in the lung tumor microenvironment. Cancer Res. 76:999–1008. 2016. View Article : Google Scholar : PubMed/NCBI

105 

Knetki-Wróblewska M, Wojas-Krawczyk K, Krawczyk P and Krzakowski M: Emerging insights into STK11, KEAP1 and KRAS mutations: Implications for immunotherapy in patients with advanced non-small cell lung cancer. Transl Lung Cancer Res. 13:3718–3730. 2024. View Article : Google Scholar : PubMed/NCBI

106 

Wei K, Sun T, Feng X, Chen Y, Liu Q and Tang H: PD-1/L1 immune checkpoint inhibitors for KRAS-mutant non-small cell lung cancer: A multicenter retrospective real-world study. BMC Cancer. 25:4442025. View Article : Google Scholar : PubMed/NCBI

107 

Dong ZY and Wu YL: What is the significance of TP53 and KRAS mutation for immunotherapy in non-small cell lung cancer? Transl Cancer Res. 6 (Suppl 6):S1115–S1117. 2017. View Article : Google Scholar

108 

Budczies J, Romanovsky E, Kirchner M, Neumann O, Blasi M, Schnorbach J, Shah R, Bozorgmehr F, Savai R, Stiewe T, et al: KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma. Br J Cancer. 131:524–533. 2024. View Article : Google Scholar : PubMed/NCBI

109 

Bischoff P, Reck M, Overbeck T, Christopoulos P, Rittmeyer A, Lüders H, Kollmeier J, Kulhavy J, Kemper M, Reinmuth N, et al: Outcome of first-line treatment with pembrolizumab according to KRAS/TP53 mutational status for nonsquamous programmed death-ligand 1-high (≥50%) NSCLC in the German national network genomic medicine lung cancer. J Thorac Oncol. 19:803–817. 2024. View Article : Google Scholar : PubMed/NCBI

110 

Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, et al: STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 8:822–835. 2018. View Article : Google Scholar : PubMed/NCBI

111 

Sun L, Handorf EA, Zhou Y, Borghaei H, Aggarwal C and Bauman J: Outcomes in patients treated with frontline immune checkpoint inhibition (ICI) for advanced NSCLC with KRAS mutations and STK11/KEAP1 comutations across PD-L1 levels. Lung Cancer. 190:1075102024. View Article : Google Scholar : PubMed/NCBI

112 

Ricciuti B and Garassino MC: Precision immunotherapy for STK11/KEAP1-mutant NSCLC. J Thorac Oncol. 19:877–882. 2024. View Article : Google Scholar : PubMed/NCBI

113 

De Giglio A, De Biase D, Favorito V, Maloberti T, Di Federico A, Zacchini F, Venturi G, Parisi C, Gustavo Dall'Olio F, Ricciotti I, et al: STK11 mutations correlate with poor prognosis for advanced NSCLC treated with first-line immunotherapy or chemo-immunotherapy according to KRAS, TP53, KEAP1, and SMARCA4 status. Lung Cancer. 199:1080582025. View Article : Google Scholar : PubMed/NCBI

114 

Negrao MV, Paula AG, Molkentine D, Hover L, Nilsson M, Vokes N, Engstrom L, Calinisan A, Briere DM, Waters L, et al: Impact of co-mutations and transcriptional signatures in non-small cell lung cancer patients treated with adagrasib in the KRYSTAL-1 trial. Clin Cancer Res. 31:1069–1081. 2025. View Article : Google Scholar : PubMed/NCBI

115 

Olsen A, Lebedeva A, Nosova P, Nikulin V, Sharova M, Ignatova E, Mileyko V and Ivanov M: Impact of the STK11/KRAS co-mutation on the response to immunotherapy in a real-world pan-cancer cohort. Tumori. 110:146–152. 2024. View Article : Google Scholar : PubMed/NCBI

116 

Sisca L, Cascetta P, Aijaz A, Catania C, Facchinetti F, Naqash AR, Ricciuti B and Cortellini A: KRAS and STK11 co-mutations in resectable non-small cell lung cancer: Enduring prognostic value and impaired immunotherapy response. Transl Lung Cancer Res. 14:2374–2382. 2025. View Article : Google Scholar : PubMed/NCBI

117 

Hellyer JA, Padda SK, Diehn M and Wakelee HA: Clinical implications of KEAP1-NFE2L2 mutations in NSCLC. J Thorac Oncol. 16:395–403. 2021. View Article : Google Scholar : PubMed/NCBI

118 

Tian L, Liu C, Zheng S, Shi H, Wei F, Jiang W, Dong Y, Xu H, Yin E, Sun N, et al: KEAP1 mutations as key crucial prognostic biomarkers for resistance to KRAS-G12C inhibitors. J Transl Med. 23:822025. View Article : Google Scholar : PubMed/NCBI

119 

Jänne PA, van den Heuvel MM, Barlesi F, Cobo M, Mazieres J, Crinò L, Orlov S, Blackhall F, Wolf J, Garrido P, et al: Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non-small cell lung cancer. JAMA. 317:1844–1853. 2017. View Article : Google Scholar : PubMed/NCBI

120 

Sreter KB, Catarata MJ, von Laffert M and Frille A: Resistance to KRAS inhibition in advanced non-small cell lung cancer. Front Oncol. 14:13578982024. View Article : Google Scholar : PubMed/NCBI

121 

Blaquier JB, Cardona AF and Recondo G: Resistance to KRASG12C inhibitors in non-small cell lung cancer. Front Oncol. 11:7875852021. View Article : Google Scholar : PubMed/NCBI

122 

Cascetta P, Marinello A, Lazzari C, Gregorc V, Planchard D, Bianco R, Normanno N and Morabito A: KRAS in NSCLC: State of the art and future perspectives. Cancers (Basel). 14:54302022. View Article : Google Scholar : PubMed/NCBI

123 

Chour A, Toffart AC, Berton E and Duruisseaux M: Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer. Front Oncol. 14:13287282024. View Article : Google Scholar : PubMed/NCBI

124 

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

125 

Mohanty A, Nam A, Srivastava S, Jones J, Lomenick B, Singhal SS, Guo L, Cho H, Li A, Behal A, et al: Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer. Sci Adv. 9:eade38162023. View Article : Google Scholar : PubMed/NCBI

126 

Akhave NS, Biter AB and Hong DS: Mechanisms of resistance to KRASG12C-targeted therapy. Cancer Discov. 11:1345–1352. 2021. View Article : Google Scholar : PubMed/NCBI

127 

Labrie M, Brugge JS, Mills GB and Zervantonakis IK: Therapy resistance: Opportunities created by adaptive responses to targeted therapies in cancer. Nat Rev Cancer. 22:323–339. 2022. View Article : Google Scholar : PubMed/NCBI

128 

Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, et al: Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 29 (Suppl 4):iv192–iv237. 2018. View Article : Google Scholar : PubMed/NCBI

129 

Seo KY, Jelinsky SA and Loechler EL: Factors that influence the mutagenic patterns of DNA adducts from chemical carcinogens. Mutat Res. 463:215–246. 2000. View Article : Google Scholar : PubMed/NCBI

130 

Goulding RE, Chenoweth M, Carter GC, Boye ME, Sheffield KM, John WJ, Leusch MS, Muehlenbein CE, Li L, Jen MH, et al: KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis. Cancer Treat Res Commun. 24:1002002020.PubMed/NCBI

131 

Awad MM, Gadgeel SM, Borghaei H, Patnaik A, Yang JC, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Altan M, et al: Long-term overall survival from KEYNOTE-021 cohort G: Pemetrexed and carboplatin with or without pembrolizumab as first-line therapy for advanced nonsquamous NSCLC. J Thorac Oncol. 16:162–168. 2021. View Article : Google Scholar : PubMed/NCBI

132 

Feng W: Advancements in targeted therapies based on the EGFR, and KRAS genetic mutations in lung cancer. Theor Nat Sci. 67:22–29. 2024. View Article : Google Scholar

133 

Harris E and Thawani R: Current perspectives of KRAS in non-small cell lung cancer. Curr Probl Cancer. 51:1011062024. View Article : Google Scholar : PubMed/NCBI

134 

Jiang Z: A review of KRAS inhibitors and potential improvement in the future. Transact Mater Biotechnol Life Sci. 7:322–327. 2024.

135 

Ricciuti B, Leonardi GC, Metro G, Grignani F, Paglialunga L, Bellezza G, Baglivo S, Mencaroni C, Baldi A, Zicari D and Crinò L: Targeting the KRAS variant for treatment of non-small cell lung cancer: Potential therapeutic applications. Expert Rev Respir Med. 10:53–68. 2016. View Article : Google Scholar : PubMed/NCBI

136 

Rosner S, Connor S, Sanber K, Zahurak M, Zhang T, Gurumurthy I, Zeng Z, Presson B, Singh D, Rayes R, et al: Divergent clinical and immunologic outcomes based on STK11 co-mutation status in resectable KRAS-mutant lung cancers following neoadjuvant immune checkpoint blockade. Clin Cancer Res. 31:339–351. 2025. View Article : Google Scholar : PubMed/NCBI

137 

Choi J, Goulding SP, Conn BP, McGann CD, Dietze JL, Kohler J, Lenkala D, Boudot A, Rothenberg DA, Turcott PJ, et al: Systematic discovery and validation of T cell targets directed against oncogenic KRAS mutations. Cell Rep Methods. 1:1000842021. View Article : Google Scholar : PubMed/NCBI

138 

Gondal MN, Cieslik M and Chinnaiyan AM: Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients. Sci Data. 12:1392025. View Article : Google Scholar : PubMed/NCBI

139 

Álvarez-Pérez JC, Sanjuán-Hidalgo J, Arenas AM, Hernández-Navas I, Benitez-Cantos MS, Andrades A, Calabuig-Fariñas S, Jantus-Lewintre E, Paz-Ares L, Ferrer I and Medina PP: High-fidelity Cas9-mediated targeting of KRAS driver mutations restrains lung cancer in preclinical models. Nat Commun. 16:70802025. View Article : Google Scholar : PubMed/NCBI

140 

Wang Y, Bui TA, Yang X, Hutvagner G and Deng W: Advancements in gene therapies targeting mutant KRAS in cancers. Cancer Metastasis Rev. 44:242025. View Article : Google Scholar : PubMed/NCBI

141 

Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, et al: Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial. Lancet. 393:1819–1830. 2019. View Article : Google Scholar : PubMed/NCBI

142 

Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al: Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 373:1627–1639. 2015. View Article : Google Scholar : PubMed/NCBI

143 

Rodríguez-Abreu D, Powell SF, Hochmair MJ, Gadgeel S, Esteban E, Felip E, Speranza G, De Angelis F, Dómine M, Cheng SY, et al: Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: Protocol-specified final analysis from KEYNOTE-189. Ann Oncol. 32:881–895. 2021. View Article : Google Scholar : PubMed/NCBI

144 

Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, et al: Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 378:2288–2301. 2018. View Article : Google Scholar : PubMed/NCBI

145 

Garassino MC, Theelen WSME, Jänne PA, Boom LN, De Marinis F, Dómine Gómez M, Nadal E, Paz-Ares L, Gu W, Felip E, et al: 5MO: First-line adagrasib (ADA) with pembrolizumab (PEMBRO) in patients (pts) with advanced/metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) and PD-L1 ≥50% from the phase II portion of KRYSTAL-7. J Thorac Oncol. 20 (Suppl 1):S8–S10. 2025. View Article : Google Scholar

146 

Neal J, Pavlakis N, Kim SW, Goto Y, Lim SM, Mountzios G, Fountzilas E, Mochalova A, Christoph DC, Bearz A, et al: CONTACT-01: A randomized phase III trial of atezolizumab + cabozantinib versus docetaxel for metastatic non-small cell lung cancer after a checkpoint inhibitor and chemotherapy. J Clin Oncol. 42:2393–2403. 2024. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sharma U, Song J, Kandu H, Zhu Y and Dai Z: Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review). Oncol Rep 55: 39, 2026.
APA
Sharma, U., Song, J., Kandu, H., Zhu, Y., & Dai, Z. (2026). Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review). Oncology Reports, 55, 39. https://doi.org/10.3892/or.2026.9044
MLA
Sharma, U., Song, J., Kandu, H., Zhu, Y., Dai, Z."Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)". Oncology Reports 55.3 (2026): 39.
Chicago
Sharma, U., Song, J., Kandu, H., Zhu, Y., Dai, Z."Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)". Oncology Reports 55, no. 3 (2026): 39. https://doi.org/10.3892/or.2026.9044
Copy and paste a formatted citation
x
Spandidos Publications style
Sharma U, Song J, Kandu H, Zhu Y and Dai Z: Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review). Oncol Rep 55: 39, 2026.
APA
Sharma, U., Song, J., Kandu, H., Zhu, Y., & Dai, Z. (2026). Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review). Oncology Reports, 55, 39. https://doi.org/10.3892/or.2026.9044
MLA
Sharma, U., Song, J., Kandu, H., Zhu, Y., Dai, Z."Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)". Oncology Reports 55.3 (2026): 39.
Chicago
Sharma, U., Song, J., Kandu, H., Zhu, Y., Dai, Z."Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)". Oncology Reports 55, no. 3 (2026): 39. https://doi.org/10.3892/or.2026.9044
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