ALK-positive non-small cell lung cancer: Mechanisms of resistance and emerging treatment options

Cancer

Volumn 120, Issue 16, 2014, Pages 2392-2402

  Steuer, Conor E ^a   Ramalingam, Suresh S ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

anaplastic lymphoma kinase; crizotinib; EML4 ALK; LDK378; non small cell lung cancer; resistance; targeted therapy

Indexed keywords

ALECTINIB; ANAPLASTIC LYMPHOMA KINASE; AP 26113; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; CERITINIB; CREATININE; CRIZOTINIB; DACOMITINIB; DOCETAXEL; ECHINODERM MICROTUBULE ASSOCIATED PROTEIN LIKE 4 ANAPLASTIC LYMPHOMA KINASE FUSION PROTEIN; GANETESPIB; HEAT SHOCK PROTEIN 90 INHIBITOR; HYBRID PROTEIN; LUMINESPIB; PEMETREXED; PROTEIN TYROSINE KINASE INHIBITOR; RETASPIMYCIN; RO 5424802; TSR 011; UNCLASSIFIED DRUG; PROTEIN TYROSINE KINASE;

ABNORMAL LABORATORY RESULT; ADVANCED CANCER; ALOPECIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; CANCER CONTROL; CANCER PATIENT; CANCER RESISTANCE; CANCER STAGING; CONSTIPATION; DECREASED APPETITE; DIARRHEA; DIZZINESS; DRUG APPROVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSGEUSIA; DYSPNEA; EDEMA; FATIGUE; FOOD AND DRUG ADMINISTRATION; GENE REARRANGEMENT; GENE TRANSLOCATION; GENETIC ANALYSIS; GENETIC VARIABILITY; HUMAN; LUNG NON SMALL CELL CANCER; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY (TOPIC); NAUSEA; NONHUMAN; OUTCOME ASSESSMENT; PERSONALIZED MEDICINE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; POINT MUTATION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECOMMENDED DRUG DOSE; REVIEW; SALVAGE THERAPY; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; VISUAL DISORDER; VOMITING; ANIMAL; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE; ENZYMOLOGY; LUNG NEOPLASMS; METABOLISM; PATHOLOGY;

ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; RECEPTOR PROTEIN-TYROSINE KINASES;

EID: 84905579152     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.28597     Document Type: Review

References (61)

1. National Cancer Institute. Lung cancer fact sheet. Available at: http://www.cancer.gov/cancertopics/types/lung. Accessed January 30, 2014.
2. Scagliotti GV, De Marinis F, Rinaldi M, et al. Phase III randomized trial comparing 3 platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002; 20: 4285-4291.
3. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497-1500.
4. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007; 448: 561-566.
5. Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008; 14: 4275-4283.
6. Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res. 2009; 15: 5216-5223.
7. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008; 3: 13-17.
8. Martelli MP, Sozzi G, Hernandez L, et al. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. Am J Pathol. 2009; 174: 661-670.
9. Perner S, Wagner PL, Demichelis F, et al. EML4-ALK fusion lung cancer: a rare acquired event. Neoplasia. 2008; 10: 298-302.
10. Shinmura K, Kageyama S, Tao H, et al. EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer. 2008; 61: 163-169.
11. Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013; 19: 4273-4281.
12. Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009; 115: 1723-1733.
13. Koh Y, Kim DW, Kim TM, et al. Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors. J Thorac Oncol. 2011; 6: 905-912.
14. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007; 131: 1190-1203.
15. Boland JM, Erdogan S, Vasmatzis G, et al. Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas. Hum Pathol. 2009; 40: 1152-1158.
16. Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res. 2008; 14: 6618-6624.
17. Zhang X, Zhang S, Yang X, et al. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression [serial online]. Mol Cancer. 2010; 9: 188.
18. Sun Y, Ren Y, Fang Z, et al. Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol. 2010; 28: 4616-4620.
19. Camidge DR, Kono SA, Flacco A, et al. Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clin Cancer Res. 2010; 16: 5581-5590.
20. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009; 27: 4247-4253.
21. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer Nat Med. 2012; 18: 378-381.
22. Kimura H, Nakajima T, Takeuchi K, et al. ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity. Lung Cancer. 2012; 75: 66-72.
23. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363: 1693-1703.
24. Conklin CM, Craddock KJ, Have C, Laskin J, Couture C, Ionescu DN,. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. 2013; 8: 45-51.
25. Camidge DR, Bang YJ, Kwak EL, 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. 2012; 13: 1011-1019.
26. Shaw AT, Kim D-W, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368: 2385-2394.
27. Ou S, Bang YJ, Camidge DR, et al. Efficacy and safety of crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2013; 31 (suppl). Abstract 8032.
28. Weickhardt AJ, Doebele RC, Purcell WT, et al. Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients. Cancer. 2013; 119: 2383-2390.
29. Lee JO, Kim TM, Lee SH, et al. Anaplastic lymphoma kinase translocation: a predictive biomarker of pemetrexed in patients with non-small cell lung cancer. J Thorac Oncol. 2011; 6: 1474-1480.
30. Camidge DR, Kono SA, Lu X, et al. Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progression-free survival on pemetrexed. J Thorac Oncol. 2011; 6: 774-780.
31. Berge EM, Lu X, Maxson D, et al. Clinical benefit from pemetrexed before and after crizotinib exposure and from crizotinib before and after pemetrexed exposure in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. Clin Lung Cancer. 2013; 14: 636-643.
32. Gandara D, Huang E, Desai S, et al. Thymidylate synthase (TS) gene expression in patients with ALK positive (+) non-small cell lung cancer (NSCLC): implications for therapy [abstract]. J Clin Oncol. 2012; 30 (suppl). Abstract 7582.
33. Suda K, Onozato R, Yatabe Y, Mitsudomi T,. EGFR T790M mutation: a double role in lung cancer cell survival? J Thorac Oncol. 2009; 4: 1-4.
34. Bixby D, Talpaz M,. Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology Am Soc Hematol Educ Program. 2009: 461-476.
35. Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010; 363: 1734-1739.
36. Sasaki T, Koivunen J, Ogino A, et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011; 71: 6051-6060.
37. Heuckmann JM, Holzel M, Sos ML, et al. ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res. 2011; 17: 7394-7401.
38. Doebele RC, Pilling AB, Aisner DL, et al. mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012; 18: 1472-1482.
39. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers [serial online]. Sci Transl Med. 2012; 4: 120ra117.
40. Kim S, Kim TM, Kim DW, et al. Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer. J Thorac Oncol. 2013; 8: 415-422.
41. Sun HY, Ji FQ,. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK. Biochem Biophys Res Commun. 2012; 423: 319-324.
42. Shaw AT, Mehra R, Kim D-W, et al. Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC [abstract]. J Clin Oncol. 2013; 21 (suppl). Abstract 8010.
43. Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol. 2013; 14: 590-598.
44. Inoue A, Nishio M, Kiura K, et al. One-year follow-up of a phase I/II study of a highly selective ALK inhibitor CH5424802/RO5424802 in ALK-rearranged advanced non-small cell lung cancer [abstract P3.11-034]. Paper presented at: International Association for the Study of Lung Cancer (IASLC) 15th World Conference on Lung Cancer; October 27-30, 2013; Sydney, Australia.
45. Ou S, Gadgeel S, Chiappori A, et al. Safety and efficacy of RO5424802/CH5424802 in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients who have failed crizotinib in a dose finding phase I study. Paper presented at: EECO European Cancer Congress 2013 (ECCO); September 27 to October 1, 2013; Amsterdam, the Netherlands.
46. Camidge DR, Bazhenova L, Salgia R, et al. Updated results of a first-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies [abstract MO067.06]. Paper presented at: International Association for the Study of Lung Cancer (IASLC) 15th World Conference on Lung Cancer; October 27-31, 2013.
47. Sequist LV, Gettinger S, Senzer NN, et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010; 28: 4953-4960.
48. Socinski MA, Goldman J, El-Hariry I, et al. A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin Cancer Res. 2013; 19: 3068-3077.
49. Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of C-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007; 67: 4408-4417.
50. Chen J, Jiang C, Wang S,. LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor. J Med Chem. 2013; 56: 5673-5674.
51. Sakamoto H, Tsukaguchi T, Hiroshima S, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011; 19: 679-690.
52. National Institutes of Health. A clinical study testing the safety and efficacy of CH5424802/RO5424802 in patients with ALK positive non-small cell lung cancer. Available at: http://clinicaltrials.gov/show/NCT01588028. Accessed January 30, 2014.
53. Zhang S, Wang F, Keats J, et al. AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066 (PF1066) [abstract LB-298]. Paper presented at: 101st Annual Meeting of the American Association for Cancer Res.; April 17-21, 2010; Washington, DC.
54. Miret JJ, Wang F, Anjum R, et al. AP26113, a potent ALK inhibitor, is also active against EGFR T790M in mouse models of NSCLC [abstract MO11.12]. Paper presented at: International Association for the Study of Lung Cancer (IASLC) 14th World Conference on Lung Cancer; July 3-7, 2011; Amsterdam, the Netherlands.
55. Weiss GJ, Sachdev J, Infante J, et al. TSR-011: a potent inhibitor of ALK including crizotinib-resistant mutations in phase 1-2 development for ALK+ NSCLC [abstract P1.11-049]. Paper presented at: International Association for the Study of Lung Cancer (IASLC) 15th World Conference on Lung Cancer; October 27-31, 2013; Sydney, Australia.
56. Neckers L,. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med. 2002; 8: S55-S61.
57. Chen Z, Sasaki T, Tan X, et al. Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010; 70: 9827-9836.
58. National Institutes of Health. A study of ganetespib in subjects with ALK-positive non-small-cell lung cancer (NSCLC) (CHIARA). Available at: http://clinicaltrials.gov/show/NCT01562015. Accessed January 30, 2014.
59. National Institutes of Health. A study of combined c-MET inhibitor and PAN-HER inhibitor (PF-02341066 and PF-00299804) in patients with non-small cell lung cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT01121575. Accessed January 30, 2014.
60. National Institutes of Health. Phase Ib study of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer. Available at: http://clinicaltrials. gov/show/NCT01772797. Accessed January 30, 2014.
61. Ou S, Riely G, Tang Y, et al. Clinical benefit of continuing crizotinib beyond initial disease progression in patients with advanced ALK-positive non-small-cell lung cancer [abstract MO07.01]. Paper presented at: 15th World Conference on Lung Cancer; October 27-30, 2013; Sydney, Australia.