Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells

Pigment Cell and Melanoma Research

Volumn 26, Issue 4, 2013, Pages 518-526

  Todd, Jason R ^a   Becker, Therese M ^a   Kefford, Richard F ^a,b   Rizos, Helen ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b MELANOMA INSTITUTE AUSTRALIA   (Australia)

Author keywords

C Kit; Imatinib; Melanoma; Nilotinib; Resistance

Indexed keywords

DASATINIB; IMATINIB; MITOGEN ACTIVATED PROTEIN KINASE; NILOTINIB; PHOSPHATIDYLINOSITOL 3 KINASE; SUNITINIB;

APOPTOSIS; ARTICLE; CANCER RESISTANCE; COMPETITIVE INHIBITION; ENZYME INHIBITION; GENE MUTATION; MELANOMA; MELANOMA CELL; NUCLEOTIDE SEQUENCE; ONCOGENE C KIT; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BENZAMIDES; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; HEK293 CELLS; HUMANS; INHIBITORY CONCENTRATION 50; LENTIVIRUS; MELANOMA; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; PYRIMIDINES; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION;

EID: 84879783591     PISSN: 17551471     EISSN: 1755148X     Source Type: Journal    
DOI: 10.1111/pcmr.12107     Document Type: Article

References (54)

1. Antonescu, C.R., Besmer, P., Guo, T. et al. (2005). Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin. Cancer Res. 11, 4182-4190.
2. Antonescu, C.R., Busam, K.J., Francone, T.D. et al. (2007). L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int. J. Cancer 121, 257-264.
3. Ashman, L.K., and Griffith, R. (2013). Therapeutic targeting of c-KIT in cancer. Expert Opin. Investig. Drugs 22, 103-115.
4. Azam, M., Latek, R.R., and Daley, G.Q. (2003). Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112, 831-843.
5. Beadling, C., Jacobson-Dunlop, E., Hodi, F.S. et al. (2008). KIT gene mutations and copy number in melanoma subtypes. Clin. Cancer Res. 14, 6821-6828.
6. Blanke, C.D., Demetri, G.D., Von Mehren, M. et al. (2008). Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J. Clin. Oncol. 26, 620-625.
7. Carter, T.A., Wodicka, L.M., Shah, N.P. et al. (2005). Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc. Natl Acad. Sci. USA 102, 11011-11016.
8. Carvajal, R.D., Antonescu, C.R., Wolchok, J.D. et al. (2011). KIT as a therapeutic target in metastatic melanoma. JAMA 305, 2327-2334.
9. Chen, L.L., Trent, J.C., Wu, E.F. et al. (2004). A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res. 64, 5913-5919.
10. Cho, J.H., Kim, K.M., Kwon, M., Kim, J.H., and Lee, J. (2011). Nilotinib in patients with metastatic melanoma harboring KIT gene aberration. Invest. New Drugs 30, 2008-2014.
11. Chou, T.C., and Talalay, P. (1984). Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55.
12. Conca, E., Negri, T., Gronchi, A., Fumagalli, E., Tamborini, E., Pavan, G.M., Fermeglia, M., Pierotti, M.A., Pricl, S., and Pilotti, S. (2009). Activate and resist: L576P-KIT in GIST. Mol. Cancer Ther. 8, 2491-2495.
13. Corless, C.L., and Heinrich, M.C. (2008). Molecular pathobiology of gastrointestinal stromal sarcomas. Annu. Rev. Pathol. 3, 557-586.
14. Cullinane, C., Natoli, A., Hui, Y., Conus, N., Jackson, S., Bruggen, J., Manley, P.W., and McArthur, G.A. (2010). Preclinical evaluation of nilotinib efficacy in an imatinib-resistant KIT-driven tumor model. Mol. Cancer Ther. 9, 1461-1468.
15. Curtin, J.A., Fridlyand, J., Kageshita, T. et al. (2005). Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353, 2135-2147.
16. Curtin, J.A., Busam, K., Pinkel, D., and Bastian, B.C. (2006). Somatic activation of KIT in distinct subtypes of melanoma. J. Clin. Oncol. 24, 4340-4346.
17. Debiec-Rychter, M., Cools, J., Dumez, H. et al. (2005). Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 128, 270-279.
18. Duensing, A., Medeiros, F., McConarty, B., Joseph, N.E., Panigrahy, D., Singer, S., Fletcher, C.D., Demetri, G.D., and Fletcher, J.A. (2004). Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene 23, 3999-4006.
19. Engelman, J.A., Zejnullahu, K., Mitsudomi, T. et al. (2007). MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043.
20. Falchook, G.S., Lewis, K.D., Infante, J.R. et al. (2012). Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 13, 782-789.
21. Garrido, M.C., and Bastian, B.C. (2010). KIT as a therapeutic target in melanoma. J. Invest. Dermatol. 130, 20-27.
22. Gately, K., O'Flaherty, J., Cappuzzo, F., Pirker, R., Kerr, K., and O'Byrne, K. (2012). The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. J. Clin. Pathol. 65, 1-7.
23. Gounder, M.M., and Maki, R.G. (2011). Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chemother. Pharmacol. 67(Suppl. 1), S25-S43.
24. Guo, J., Si, L., Kong, Y. et al. (2011). Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J. Clin. Oncol. 29, 2904-2909.
25. Haferkamp, S., Scurr, L.L., Becker, T.M., Frausto, M., Kefford, R.F., and Rizos, H. (2009). Oncogene-induced senescence does not require the p16(INK4a) or p14ARF melanoma tumor suppressors. J. Invest. Dermatol. 129, 1983-1991.
26. Handolias, D., Hamilton, A.L., Salemi, R., Tan, A., Moodie, K., Kerr, L., Dobrovic, A., and McArthur, G.A. (2010). Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT. Br. J. Cancer 102, 1219-1223.
27. Heinrich, M.C., Corless, C.L., Blanke, C.D. et al. (2006). Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J. Clin. Oncol. 24, 4764-4774.
28. Heinrich, M.C., Maki, R.G., Corless, C.L. et al. (2008). Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J. Clin. Oncol. 26, 5352-5359.
29. Liang, R., Wallace, A.R., Schadendorf, D., and Rubin, B.P. (2011). The phosphatidyl inositol 3-kinase pathway is central to the pathogenesis of Kit-activated melanoma. Pigment Cell Melanoma Res. 24, 714-723.
30. Liegl, B., Kepten, I., Le, C., Zhu, M., Demetri, G.D., Heinrich, M.C., Fletcher, C.D.M., Corless, C.L., and Fletcher, J.A. (2008). Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J. Pathol. 216, 64-74.
31. Liegl-Atzwanger, B., Fletcher, J.A., and Fletcher, C.D. (2010). Gastrointestinal stromal tumors. Virchows Arch. 456, 111-127.
32. Minor, D.R., Kashani-Sabet, M., Garrido, M., O'Day, S.J., Hamid, O., and Bastian, B.C. (2012). Sunitinib therapy for melanoma patients with KIT mutations. Clin. Cancer Res. 18, 1457-1463.
33. Miranda, C., Nucifora, M., Molinari, F. et al. (2012). KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin. Cancer Res. 18, 1769-1776.
34. Nazarian, R., Shi, H., Wang, Q. et al. (2010). Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977.
35. Ou, W.B., Zhu, M.J., Demetri, G.D., Fletcher, C.D.M., and Fletcher, J.A. (2008). Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors. Oncogene 27, 5624-5634.
36. Prenen, H., Cools, J., Mentens, N., Folens, C., Sciot, R., Schoffski, P., Van Oosterom, A., Marynen, P., and Debiec-Rychter, M. (2006). Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res. 12, 2622-2627.
37. Rivera, R.S., Nagatsuka, H., Gunduz, M., Cengiz, B., Gunduz, E., Siar, C.H., Tsujigiwa, H., Tamamura, R., Han, K.N., and Nagai, N. (2008). C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma. Virchows Arch. 452, 27-32.
38. Ruano, I., and Izquierdo, M. (2009). Selective RNAi-mediated inhibition of mutated c-kit. J. RNAi Gene Silencing 5, 339-344.
39. Rubin, B.P., Heinrich, M.C., and Corless, C.L. (2007). Gastrointestinal stromal tumour. Lancet 369, 1731-1741.
40. Satzger, I., Schaefer, T., Kuettler, U., Broecker, V., Voelker, B., Ostertag, H., Kapp, A., and Gutzmer, R. (2008). Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas. Br. J. Cancer 99, 2065-2069.
41. Sawaki, A., Nishida, T., Doi, T., Yamada, Y., Komatsu, Y., Kanda, T., Kakeji, Y., Onozawa, Y., Yamasaki, M., and Ohtsu, A. (2011). Phase 2 study of nilotinib as third-line therapy for patients with gastrointestinal stromal tumor. Cancer 117, 4633-4641.
42. Schirosi, L., Nannini, N., Nicoli, D. et al. (2012). Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors. Ann. Oncol. 23, 2409-2414.
43. Schittenhelm, M.M., Shiraga, S., Schroeder, A., Corbin, A.S., Griffith, D., Lee, F.Y., Bokemeyer, C., Deininger, M.W., Druker, B.J., and Heinrich, M.C. (2006). Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 66, 473-481.
44. Shimizu, T., Tolcher, A.W., Papadopoulos, K.P. et al. (2012). The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin. Cancer Res. 18, 2316-2325.
45. Si, L., Xu, X., Kong, Y. et al. (2012). Major response to everolimus in melanoma with acquired imatinib resistance. J. Clin. Oncol. 30, e37-e40.
46. Siddiqui, M.A., and Scott, L.J. (2007). Imatinib: a review of its use in the management of gastrointestinal stromal tumours. Drugs 67, 805-820.
47. Sleijfer, S., Wiemer, E., Seynaeve, C., and Verweij, J. (2007). Improved insight into resistance mechanisms to imatinib in gastrointestinal stromal tumors: a basis for novel approaches and individualization of treatment. Oncologist 12, 719-726.
48. Takayama, Y., Kokuryo, T., Yokoyama, Y., Nagino, M., Nimura, Y., Senga, T., and Hamaguchi, M. (2008). MEK inhibitor enhances the inhibitory effect of imatinib on pancreatic cancer cell growth. Cancer Lett. 264, 241-249.
49. Todd, J.R., Scurr, L.L., Becker, T.M., Kefford, R.F., and Rizos, H. (2012). The MAPK pathway functions as a redundant survival signal that reinforces the PI3K cascade in c-Kit mutant melanoma. Oncogene. doi: 10.1038/onc.2012.562. (in press).
50. Villanueva, J., Vultur, A., Lee, J.T. et al. (2010). Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 18, 683-695.
51. Wang, W.-L., Conley, A., Reynoso, D., Nolden, L., Lazar, A.J., George, S., and Trent, J.C. (2011). Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor. Cancer Chemother. Pharmacol. 67(Suppl. 1), S15-S24.
52. Wardelmann, E., Merkelbach-Bruse, S., Pauls, K. et al. (2006). Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin. Cancer Res. 12, 1743-1749.
53. Weber, J.S., Flaherty, K.T., Infante, J.R. et al. (2012). Updated safety and efficacy results from a phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naive metastatic melanoma. J. Clin. Oncol. 30, 8510-8510.
54. Woodman, S.E., Trent, J.C., Stemke-Hale, K. et al. (2009). Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol. Cancer Ther. 8, 2079-2085.