Role of STK11 in ALK‑positive non‑small cell lung cancer (Review)
- Authors:
- Wen Zhou
- Lu-Da Yan
- Zhi-Qiong Yu
- Na Li
- Yong-Hua Yang
- Meng Wang
- Yuan-Yuan Chen
- Meng-Xia Mao
- Xiao-Chun Peng
- Jun Cai
-
Affiliations: Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434023, P.R. China, Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, P.R. China - Published online on: April 15, 2022 https://doi.org/10.3892/ol.2022.13301
- Article Number: 181
-
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
|
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 | |
|
Ye Z, Huang Y, Ke J, Zhu X, Leng S and Luo H: Breakthrough in targeted therapy for non-small cell lung cancer. Biomed Pharmacother. 133:1110792021. View Article : Google Scholar : PubMed/NCBI | |
|
Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Yang L, Li N, Wang M, Zhang YH, Yan LD, Zhou W, Yu ZQ, Peng XC and Cai J: Tumorigenic effect of TERT and its potential therapeutic target in NSCLC (Review). Oncol Rep. 46:1822021. View Article : Google Scholar : PubMed/NCBI | |
|
Brueckl WM, Ficker JH and Zeitler G: Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). BMC Cancer. 20:11852020. View Article : Google Scholar : PubMed/NCBI | |
|
Imyanitov EN, Iyevleva AG and Levchenko EV: Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives. Crit Rev Oncol Hematol. 157:1031942021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu J, Li D, Luo H and Zhu X: Circular RNAs: The star molecules in cancer. Mol Aspects Med. 70:141–152. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Guo B, Li D, Du L and Zhu X: piRNAs: Biogenesis and their potential roles in cancer. Cancer Metastasis Rev. 39:567–575. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Gerlinger M: Targeted drugs ramp up cancer mutability. Science. 366:1452–1453. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Liang G, Fan W, Luo H and Zhu X: The emerging roles of artificial intelligence in cancer drug development and precision therapy. Biomed Pharmacother. 128:1102552020. View Article : Google Scholar : PubMed/NCBI | |
|
Li S, Zhang Z, Lai WF, Cui L and Zhu X: How to overcome the side effects of tumor immunotherapy. Biomed Pharmacother. 130:1106392020. View Article : Google Scholar : PubMed/NCBI | |
|
Ceccon M, Mologni L, Bisson W, Scapozza L and Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 11:122–132. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Toyokawa G, Hirai F, Inamasu E, Yoshida T, Nosaki K, Takenaka T, Yamaguchi M, Seto T, Takenoyama M and Ichinose Y: Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib. J Thorac Oncol. 9:e86–e87. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Gainor JF, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R, Dagogo-Jack I, Gadgeel S, Schultz K, Singh M, et al: Molecular mechanisms of resistance to first- and second-generation ALK Inhibitors in ALK-rearranged lung cancer. Cancer Discov. 6:1118–1133. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Toyokawa G and Seto T: Updated evidence on the mechanisms of resistance to ALKInhibitors and strategies to overcome such resistance: Clinical and preclinical data. Oncol Res Treat. 38:291–298. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Costa DB: Clinical development and approval of second generation ALK inhibitors for ALKrearranged lung cancer. Transl Lung Cancer Res. 3:373–375. 2014.PubMed/NCBI | |
|
Roskoski R Jr: ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. Pharmacol Res. 121:202–212. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, et al: Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 370:1189–1197. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rothschild SI: New treatment options for ALK+ advanced non-small-cell lung cancer: Critical appraisal of ceritinib. Ther Clin Risk Manag. 12:735–741. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Rossi A: Alectinib for ALK-positive non-small-cell lung cancer. Expert Rev Clin Pharmacol. 9:1005–1013. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kong X, Pan P, Sun H, Xia H, Wang X, Li Y and Hou T: Drug discovery targeting anaplastic lymphoma kinase (ALK). J Med Chem. 62:10927–10954. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Qian M, Zhu B, Wang X and Liebman M: Drug resistance in ALK-positiveNon-small cell lungcancer patients. Semin Cell Dev Biol. 64:150–157. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Katayama R, Lovly CM and Shaw AT: Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: A paradigm for precision cancer medicine. Clin Cancer Res. 21:2227–2235. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Morales La Madrid A, Campbell N, Smith S, Cohn SL and Salgia R: Targeting ALK: A promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin's lymphoma, and neuroblastoma. Target Oncol. 7:199–210. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Shaw AT and Solomon B: Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res. 17:2081–2086. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Z, Sasaki T, Tan X, Carretero J, Shimamura T, Li D, Xu C, Wang Y, Adelmant GO, Capelletti M, et al: Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 70:9827–9836. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Pyo KH, Lim SM, Kim HR, Sung YH, Yun MR, Kim SM, Kim H, Kang HN, Lee JM, Kim SG, et al: Establishment of a conditional transgenic mouse model recapitulating EML4-ALK-positive human non-small cell lung cancer. J Thorac Oncol. 12:491–500. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Takeuchi K, Choi YL, Soda M, Inamura K, Togashi Y, Hatano S, Enomoto M, Takada S, Yamashita Y, Satoh Y, et al: Multiplex reverse transcription-PCR screening for EML4-ALKfusion transcripts. Clin Cancer Res. 14:6618–6624. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Sharma GG, Mota I, Mologni L, Patrucco E, Gambacorti-Passerini C and Chiarle R: Tumor resistance against ALKTargeted therapy-where it comes from and where it goes. Cancers (Basel). 10:622018. View Article : Google Scholar : PubMed/NCBI | |
|
Maddalo D, Manchado E, Concepcion CP, Bonetti C, Vidigal JA, Han YC, Ogrodowski P, Crippa A, Rekhtman N, de Stanchina E, et al: In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature. 516:423–427. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rodig SJ, Mino-Kenudson M, Dacic S, Yeap BY, Shaw A, Barletta JA, Stubbs H, Law K, Lindeman N, Mark E, et al: Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res. 15:5216–5223. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Gristina V, La Mantia M, Iacono F, Galvano A, Russo A and Bazan V: The emerging therapeutic landscape of ALK inhibitors in non-small cell lung cancer. Pharmaceuticals (Basel). 13:4742020. View Article : Google Scholar : PubMed/NCBI | |
|
Du X, Shao Y, Qin HF, Tai YH and Gao HJ: ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer. 9:423–430. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, et al: Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: Updated results from a phase 1 study. Lancet Oncol. 13:1011–1019. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Blackhall F, Ross Camidge D, Shaw AT, Soria JC, Solomon BJ, Mok T, Hirsh V, Jänne PA, Shi Y, Yang PC, et al: Final results of the large-scale multinational trial PROFILE 1005: Efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. ESMO Open. 2:e0002192017. View Article : Google Scholar : PubMed/NCBI | |
|
Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, et al: Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 50:691–700. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, et al: Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 36:2251–2258. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, et al: Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): Updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 17:452–463. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Crinò L, Ahn MJ, De Marinis F, Groen HJ, Wakelee H, Hida T, Mok T, Spigel D, Felip E, Nishio M, et al: Multicenter phase ii study of whole-body and intracranial activity with ceritinib in patients With ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: Results from ASCEND-2. J Clin Oncol. 34:2866–2873. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, et al: First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomised, open-label, phase 3 study. Lancet. 389:917–929. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, et al: Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): An open-label, randomised phase 3 trial. Lancet. 390:29–39. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Pérol M, Pavlakis N, Levchenko E, Platania M, Oliveira J, Novello S, Chiari R, Moran T, Mitry E, Nüesch E, et al: Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. Lung Cancer. 138:79–87. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Camidge DR, Dziadziuszko R, Peters S, Mok T, Noe J, Nowicka M, Gadgeel SM, Cheema P, Pavlakis N, de Marinis F, et al: Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 14:1233–1243. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, et al: Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: Second interim analysis of the phase III ALTA-1L Trial. J Clin Oncol. 38:3592–3603. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, et al: Lorlatinib in patients with ALK-positive non-small-cell lung cancer: Results from a global phase 2 Study. Lancet Oncol. 19:1654–1667. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Friboulet L, Li N, Katayama R, Lee CC, Gainor JF, Crystal AS, Michellys PY, Awad MM, Yanagitani N, Kim S, et al: The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 4:662–673. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Xia B, Nagasaka M, Zhu VW, Ou SI and Soo RA: How to select the best upfront therapy for metastatic disease? Focus on ALK-rearranged non-small cell lung cancer (NSCLC). Transl Lung Cancer Res. 9:2521–2534. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Werner MT, Zhao C, Zhang Q and Wasik MA: Nucleophosmin-anaplastic lymphoma kinase: The ultimate oncogene and therapeutic target. Blood. 129:823–831. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Tse BC, Said BI, Fan ZJ, Hueniken K, Patel D, Gill G, Liang M, Razooqi M, Brown MC, Sacher AG, et al: Longitudinal health utilities, symptoms and toxicities in patients with ALK-rearranged lung cancer treated with tyrosine kinase inhibitors: A prospective real-world assessment. Curr Oncol. 27:e552–e559. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Castellanos EH and Horn L: Re-Evaluating progression in an era of progress: A review of first- and second-line treatment options in anaplastic lymphoma kinase-positive non-small cell lung cancer. Oncologist. 21:755–761. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, et al: Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 383:1328–1339. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hallberg B and Palmer RH: The role of the ALK receptor in cancer biology. Ann Oncol. 27 (Suppl 3):iii4–iii15. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, et al: EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 363:1734–1739. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Azam M, Seeliger MA, Gray NS, Kuriyan J and Daley GQ: Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 15:1109–1118. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Heuckmann JM, Hölzel M, Sos ML, Heynck S, Balke-Want H, Koker M, Peifer M, Weiss J, Lovly CM, Grütter C, et al: ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res. 17:7394–7401. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Sasaki T, Koivunen J, Ogino A, Yanagita M, Nikiforow S, Zheng W, Lathan C, Marcoux JP, Du J, Okuda K, et al: A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 71:6051–6060. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Katayama R, Friboulet L, Koike S, Lockerman EL, Khan TM, Gainor JF, Iafrate AJ, Takeuchi K, Taiji M, Okuno Y, et al: Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 20:5686–5696. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Isozaki H, Hotta K, Ichihara E, Takigawa N, Ohashi K, Kubo T, Ninomiya T, Ninomiya K, Oda N, Yoshioka H, et al: Protocol design for the bench to bed trial in alectinib-refractory non-small-cell lung cancer patients harboring the EML4-ALK fusion gene (ALRIGHT/OLCSG1405). Clin Lung Cancer. 17:602–605. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Zou HY, Friboulet L, Kodack DP, Engstrom LD, Li Q, West M, Tang RW, Wang H, Tsaparikos K, Wang J, et al: PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 28:70–81. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, et al: Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F. N Engl J Med. 374:54–61. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, et al: Results of PROFILE 1029, a phase iii comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer. J Thorac Oncol. 13:1539–1548. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Krishnamurthy N, Goodman AM, Barkauskas DA and Kurzrock R: STK11 alterations in the pan-cancer setting: Prognostic and therapeutic implications. Eur J Cancer. 148:215–229. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wohlhieter CA, Richards AL, Uddin F, Hulton CH, Quintanal-Villalonga À, Martin A, de Stanchina E, Bhanot U, Asher M, Shah NS, et al: Concurrent mutations in STK11 and KEAP1 promote ferroptosis protection and SCD1 dependence in lung cancer. Cell Rep. 33:1084442020. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Gowans GJ, Hawley SA, Ross FA and Hardie DG: AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18:556–566. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Höglund P, et al: A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 391:184–187. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Mahoney CL, Choudhury B, Davies H, Edkins S, Greenman C, Haaften G, Mironenko T, Santarius T, Stevens C, Stratton MR and Futreal PA: LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition. Br J Cancer. 100:370–375. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Parachoniak CA, Rankin A, Gaffney B, Hartmaier R, Spritz D, Erlich RL, Miller VA, Morosini D, Stephens P, Ross JS, et al: Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring an STK11variant. Cold Spring Harb Mol Case Stud. 3:a0007782017. View Article : Google Scholar : PubMed/NCBI | |
|
Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, Westra WH, Herman JG and Sidransky D: Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 62:3659–3662. 2002.PubMed/NCBI | |
|
Hezel AF, Gurumurthy S, Granot Z, Swisa A, Chu GC, Bailey G, Dor Y, Bardeesy N and Depinho RA: Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms. Mol Cell Biol. 28:2414–2425. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Wingo SN, Gallardo TD, Akbay EA, Liang MC, Contreras CM, Boren T, Shimamura T, Miller DS, Sharpless NE, Bardeesy N, et al: Somatic LKB1 mutations promote cervical cancer progression. PLoS One. 4:e51372009. View Article : Google Scholar : PubMed/NCBI | |
|
Gill RK, Yang SH, Meerzaman D, Mechanic LE, Bowman ED, Jeon HS, Roy Chowdhuri S, Shakoori A, Dracheva T, Hong KM, et al: Frequent homozygous deletion of the LKB1/STK11gene in non-small cell lung cancer. Oncogene. 30:3784–3791. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SM, Choi JE, Na YK, Lee EJ, Lee WK, Choi YY, Yoon GS, Jeon HS, Kim DS and Park JY: Genetic and epigenetic alterations of the LKB1 gene and their associations with mutations in TP53 and EGFR pathway genes in Korean non-small cell lung cancers. Lung Cancer. 81:194–199. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Tanwar PS, Mohapatra G, Chiang S, Engler DA, Zhang L, Kaneko-Tarui T, Ohguchi Y, Birrer MJ and Teixeira JM: Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer. Carcinogenesis. 35:546–553. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Li J, Liu J, Li P, Mao X, Li W, Yang J and Liu P: Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion. J Exp Clin Cancer Res. 33:702014. View Article : Google Scholar : PubMed/NCBI | |
|
Yang JY, Jiang SH, Liu DJ, Yang XM, Huo YM, Li J, Hua R, Zhang ZG and Sun YW: Decreased LKB1 predicts poor prognosis in pancreatic ductal adenocarcinoma. Sci Rep. 5:105752015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang W, Yin L, Song G, Han X, Yin Z and Luo D: LKB1 loss cooperating with BRAFV600E promotes melanoma cell invasion and migration by up-regulation MMP-2 via PI3K/Akt/mTOR pathway. Oncotarget. 8:113847–113857. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Matsumoto S, Iwakawa R, Takahashi K, Kohno T, Nakanishi Y, Matsuno Y, Suzuki K, Nakamoto M, Shimizu E, Minna JD and Yokota J: Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene. 26:5911–5918. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Fang R, Zheng C, Sun Y, Han X, Gao B, Li C, Liu H, Wong KK, Liu XY, Chen H and Ji H: Integrative genomic analysis reveals a high frequency of LKB1 genetic alteration in Chinese lung adenocarcinomas. J Thorac Oncol. 9:254–258. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, et al: LKB1 modulates lung cancer differentiation and metastasis. Nature. 448:807–810. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Liang J and Mills GB: AMPK: A contextual oncogene or tumor suppressor? Cancer Res. 73:2929–2935. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Cancer Genome Atlas Research Network, . Comprehensive molecular profiling of lung adenocarcinoma. Nature. 511:543–550. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Baas AF, Smit L and Clevers H: LKB1 tumor suppressor protein: PARtaker in cell polarity. Trends Cell Biol. 14:312–319. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Forcet C, Etienne-Manneville S, Gaude H, Fournier L, Debilly S, Salmi M, Baas A, Olschwang S, Clevers H and Billaud M: Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity. Hum Mol Genet. 14:1283–1292. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Galan-Cobo A, Sitthideatphaiboon P, Qu X, Poteete A, Pisegna MA, Tong P, Chen PH, Boroughs LK, Rodriguez MLM, Zhang W, et al: LKB1 and KEAP1/NRF2 pathways cooperatively promote metabolic reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma. Cancer Res. 79:3251–3267. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Shackelford DB and Shaw RJ: The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression. Nat Rev Cancer. 9:563–575. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Shen Z, Wen XF, Lan F, Shen ZZ and Shao ZM: The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma. Clin Cancer Res. 8:2085–2090. 2002.PubMed/NCBI | |
|
Liu W, Monahan KB, Pfefferle AD, Shimamura T, Sorrentino J, Chan KT, Roadcap DW, Ollila DW, Thomas NE, Castrillon DH, et al: LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell. 21:751–764. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Sanchez-Cespedes M: A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene. 26:7825–7832. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Schabath MB, Welsh EA, Fulp WJ, Chen L, Teer JK, Thompson ZJ, Engel BE, Xie M, Berglund AE, Creelan BC, et al: Differential association of STK11 and TP53 with KRASmutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene. 35:3209–3216. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Lamberti G, Sisi M, Andrini E, Palladini A, Giunchi F, Lollini PL, Ardizzoni A and Gelsomino F: The mechanisms of PD-L1 regulation in non-small-cell lung cancer (NSCLC): Which are the involved players? Cancers (Basel). 12:31292020. View Article : Google Scholar : PubMed/NCBI | |
|
Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, Chang MT, Ni A, Kundra R, Jonsson P, et al: Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 7:596–609. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Roosan MR, Mambetsariev I, Pharaon R, Fricke J, Husain H, Reckamp KL, Koczywas M, Massarelli E, Bild AH and Salgia R: Usefulness of circulating tumor DNA in identifying somatic mutations and tracking tumor evolution in patients with non-small cell lung cancer. Chest. 160:1095–1107. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Dahmani R, Just PA, Delay A, Canal F, Finzi L, Prip-Buus C, Lambert M, Sujobert P, Buchet-Poyau K, Miller E, et al: A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties. Oncogene. 34:2337–2346. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Bouchekioua-Bouzaghou K, Poulard C, Rambaud J, Lavergne E, Hussein N, Billaud M, Bachelot T, Chabaud S, Mader S, Dayan G, et al: LKB1 when associated with methylatedERα is a marker of bad prognosis in breast cancer. Int J Cancer. 135:1307–1318. 2014.PubMed/NCBI | |
|
Koivunen JP, Kim J, Lee J, Rogers AM, Park JO, Zhao X, Naoki K, Okamoto I, Nakagawa K, Yeap BY, et al: Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients. Br J Cancer. 99:245–252. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Roy BC, Kohno T, Iwakawa R, Moriguchi T, Kiyono T, Morishita K, Sanchez-Cespedes M, Akiyama T and Yokota J: Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells. Lung Cancer. 70:136–145. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Yao YH, Cui Y, Qiu XN, Zhang LZ, Zhang W, Li H and Yu JM: Attenuated LKB1-SIK1 signaling promotes epithelial-mesenchymal transition and radioresistance of non-small cell lung cancer cells. Chin J Cancer. 35:502016. View Article : Google Scholar : PubMed/NCBI | |
|
Momcilovic M and Shackelford DB: Targeting LKB1 in cancer-exposing and exploiting vulnerabilities. Br J Cancer. 113:574–584. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, Leblanc M, Wei L, Fishbein MC, Czernin J, Mischel PS, et al: LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell. 23:143–158. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Dobashi Y, Watanabe Y, Miwa C, Suzuki S and Koyama S: Mammalian target of rapamycin: A central node of complex signaling cascades. Int J Clin Exp Pathol. 4:476–495. 2011.PubMed/NCBI | |
|
Saxton RA and Sabatini DM: mTOR signaling in growth, metabolism, and disease. Cell. 168:960–976. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Chen B, Tan Z, Gao J, Wu W, Liu L, Jin W, Cao Y, Zhao S, Zhang W, Qiu Z, et al: Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer. J Exp Clin Cancer Res. 34:1262015. View Article : Google Scholar : PubMed/NCBI | |
|
Krencz I, Sebestyén A, Fábián K, Márk Á, Moldvay J, Khoor A, Kopper L and Pápay J: Expression of mTORC1/2-related proteins in primary and brain metastatic lung adenocarcinoma. Hum Pathol. 62:66–73. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Seki N, Takasu T, Mandai K, Nakata M, Saeki H, Heike Y, Takata I, Segawa Y, Hanafusa T and Eguchi K: Expression of eukaryotic initiation factor 4E in atypical adenomatous hyperplasia and adenocarcinoma of the human peripheral lung. Clin Cancer Res. 8:3046–3053. 2002.PubMed/NCBI | |
|
Yoshizawa A, Fukuoka J, Shimizu S, Shilo K, Franks TJ, Hewitt SM, Fujii T, Cordon-Cardo C, Jen J and Travis WD: Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Clin Cancer Res. 16:240–248. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Jeon SM, Chandel NS and Hay N: AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature. 485:661–665. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Joo MS, Kim WD, Lee KY, Kim JH, Koo JH and Kim SG: AMPK facilitates nuclear accumulation of Nrf2 by phosphorylating at serine 550. Mol Cell Biol. 36:1931–1942. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Ciccarese F, Zulato E and Indraccolo S: LKB1/AMPK pathway and drug response in cancer: A therapeutic perspective. Oxid Med Cell Longev. 2019:87308162019. View Article : Google Scholar : PubMed/NCBI | |
|
Singh A, Daemen A, Nickles D, Jeon SM, Foreman O, Sudini K, Gnad F, Lajoie S, Gour N, Mitzner W, et al: NRF2 activation promotes aggressive lung cancer and associates with poor clinical outcomes. Clin Cancer Res. 27:877–888. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Trapp EK, Majunke L, Zill B, Sommer H, Andergassen U, Koch J, Harbeck N, Mahner S, Friedl TWP, Janni W, et al: LKB1 pro-oncogenic activity triggers cell survival in circulating tumor cells. Mol Oncol. 11:1508–1526. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA and Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA. 101:3329–3335. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Deng L, Yao P, Li L, Ji F, Zhao S, Xu C, Lan X and Jiang P: p53-mediated control of aspartate-asparagine homeostasis dictates LKB1 activity and modulates cell survival. Nat Commun. 11:17552020. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Goodman AM, Piccioni D, Kato S, Boichard A, Wang HY, Frampton G, Lippman SM, Connelly C, Fabrizio D, Miller V, et al: Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid Tumors. JAMA Oncol. 4:1237–1244. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P, et al: Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 31:1023–1031. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K and Yamamoto M: Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 24:7130–7139. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Donnelly LL, Hogan TC, Lenahan SM, Nandagopal G, Eaton JG, Lebeau MA, McCann CL, Sarausky HM, Hampel KJ, Armstrong JD, et al: Functional assessment of somatic STK11variants identified in primary human non-small cell lung cancers. Carcinogenesis. 42:1428–1438. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Gill CM, Loewenstern J, Rutland JW, Arib H, Pain M, Umphlett M, Kinoshita Y, McBride RB, Bederson J, Donovan M, et al: STK11 mutation status is associated with decreased survival in meningiomas. Neurol Sci. 41:2585–2589. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Facchinetti F, Bluthgen MV, Tergemina-Clain G, Faivre L, Pignon JP, Planchard D, Remon J, Soria JC, Lacroix L and Besse B: LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value. Lung Cancer. 112:62–68. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, et al: Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet. 389:255–265. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim DW, Han JY, Molina JR, Kim JH, Dubos Arvis C, Ahn MJ, et al: Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: An updated analysis of KEYNOTE-010 trial. Ann Oncol. 30:281–289. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zugazagoitia J, Molina-Pinelo S, Lopez-Rios F and Paz-Ares L: Biological therapies in nonsmall cell lung cancer. Eur Respir J. 49:16015202017. View Article : Google Scholar : PubMed/NCBI | |
|
Shire NJ, Klein AB, Golozar A, Collins JM, Fraeman KH, Nordstrom BL, McEwen R, Hembrough T and Rizvi NA: STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world. PLoS One. 15:e02383582020. View Article : Google Scholar : PubMed/NCBI | |
|
Mograbi B, Heeke S and Hofman P: The Importance of STK11/LKB1 assessment in non-small cell lung carcinomas. Diagnostics (Basel). 11:1962021. View Article : Google Scholar : PubMed/NCBI | |
|
Herter-Sprie GS, Korideck H, Christensen CL, Herter JM, Rhee K, Berbeco RI, Bennett DG, Akbay EA, Kozono D, Mak RH, et al: Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models. Nat Commun. 5:58702014. View Article : Google Scholar : PubMed/NCBI | |
|
He Q, Li J, Dong F, Cai C and Zou X: LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway. Mol Med Rep. 16:2205–2210. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Li N, Jiang W, Deng W, Ye R, Xu C, Qiao Y, Sharma A, Zhang M, Hung MC, et al: Mutant LKB1 confers enhanced radiosensitization in combination with trametinib in KRAS-mutant non-small cell lung cancer. Clin Cancer Res. 24:5744–5756. 2018. View Article : Google Scholar : PubMed/NCBI |
