Oncogene addiction: Pathways of therapeutic response, resistance, and road maps toward a cure

EMBO Reports

Volumn 16, Issue 3, 2015, Pages 280-296

  Pagliarini, Raymond ^a   Shao, Wenlin ^a   Sellers, William R ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

feedback; oncogene addiction; oncogenic shock; targeted therapy

Indexed keywords

CANCER CELL; CANCER RESISTANCE; GENE MUTATION; GENE TARGETING; HUMAN; MALIGNANT NEOPLASTIC DISEASE; ONCOGENE; ONCOGENE ADDICTION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; BIOLOGICAL MODEL; CELL PROLIFERATION; CELL SURVIVAL; DRUG DELIVERY SYSTEM; DRUG EFFECTS; DRUG RESISTANCE; ESSENTIAL GENE; GENETICS; NEOPLASM; PHYSIOLOGY; PROCEDURES;

ANTINEOPLASTIC AGENT;

ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; CELL SURVIVAL; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; GENES, ESSENTIAL; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; ONCOGENES;

EID: 84924061466     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.15252/embr.201439949     Document Type: Review

References (205)

1. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW, (2013) Cancer genome landscapes. Science 339: 1546-1558
2. Weinstein IB, (2002) Cancer. Addiction to oncogenes-the Achilles heal of cancer. Science 297: 63-64
3. Luo J, Solimini NL, Elledge SJ, (2009) Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 136: 823-837
4. Sharma SV, Settleman J, (2007) Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev 21: 3214-3231
5. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G, (1984) Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36: 93-99
6. Bartram CR, de Klein A, Hagemeijer A, van Agthoven T, Geurts van Kessel A, Bootsma D, Grosveld G, Ferguson-Smith MA, Davies T, Stone M, et al, (1983) Translocation of c-ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306: 277-280
7. Lugo TG, Pendergast AM, Muller AJ, Witte ON, (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247: 1079-1082
8. Daley GQ, Van Etten RA, Baltimore D, (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247: 824-830
9. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, et al, (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348: 994-1004
10. Wang ZY, Chen Z, (2008) Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 111: 2505-2515
11. Tomita A, Kiyoi H, Naoe T, (2013) Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia. Int J Hematol 97: 717-725
12. Garraway LA, Sellers WR, (2006) Lineage dependency and lineage-survival oncogenes in human cancer. Nat Rev Cancer 6: 593-602
13. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JC, et al, (2012) The mutational landscape of lethal castration-resistant prostate cancer. Nature 487: 239-243
14. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, et al, (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44: 685-689
15. Dawson MA, Kouzarides T, (2012) Cancer epigenetics: from mechanism to therapy. Cell 150: 12-27
16. Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV, Bhang HE, Taylor JE, Hu M, Englund NP, et al, (2013) Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet 45: 1386-1391
17. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, et al, (2012) EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 492: 108-112
18. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, et al, (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340: 626-630
19. Wang F, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, et al, (2013) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340: 622-626
20. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, et al, (2010) Selective inhibition of BET bromodomains. Nature 468: 1067-1073
21. Stein E, Garcia-Manero G, Rizzieri DA, Savona M, Tibes R, Altman JK, Jongen-Lavrencic M, Döhner H, Armstrong S, Pollock RM, et al, (2014) The DOT1L inhibitor EPZ-5676: safety and activity in relapsed/refractory patients with MLL-rearranged leukemia. Blood 124: 387
22. th Annual Meeting of the American Association for Cancer Research, 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; 2014. Abstract nr CT103
23. Copeland RA, Keilhack H, Italiano A, Knutson SK, Yokoi A, Kawano S, Minoshima Y, Huang KC, Warholic NM, Johnston LD, et al, (2014) EZH2 Inhibitor EPZ-6438 (E7438) in Non-Hodgkin Lymphoma: Pre-Clinical Models and Early Clinical Observations. ASH Meeting on Lymphoma Biology 2014
24. Pollyea DA, de Botton S, Fathi AT, Stein EM, Tallman MS, Agresta S, Bowden C, Fan B, Prah M, Yang H, et al, (2014) Clinical safety and activity in a phase 1 trial of AG-120, a first-in-class, potent inhibitor of the IDH1 mutant protein, in patients with IDH1 mutant positive advanced hematological malignancies. Eur J Cancer 50 (Suppl 6): 195
25. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB, (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2: 561-566
26. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL, (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876-880
27. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon y Cajal S, Arribas J, et al, (2007) Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 99: 628-638
28. Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, et al, (2011) RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 480: 387-390
29. Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, Chodon T, Guo R, Johnson DB, Dahlman KB, et al, (2014) Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 4: 80-93
30. Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, et al, (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45: 1446-1451
31. Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, Place CS, Taylor-Weiner A, Whittaker S, Kryukov GV, et al, (2014) The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 4: 94-109
32. Wagle N, Van Allen EM, Treacy DJ, Frederick DT, Cooper ZA, Taylor-Weiner A, Rosenberg M, Goetz EM, Sullivan RJ, Farlow DN, et al, (2014) MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov 4: 61-68
33. Maertens O, Johnson B, Hollstein P, Frederick DT, Cooper ZA, Messiaen L, Bronson RT, McMahon M, Granter S, Flaherty K, et al, (2013) Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov 3: 338-349
34. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N, (2010) RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464: 427-430
35. Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, Hussain J, Reis-Filho JS, Springer CJ, Pritchard C, et al, (2010) Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140: 209-221
36. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, et al, (2010) RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464: 431-435
37. Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, et al, (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104: 20932-20937
38. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al, (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316: 1039-1043
39. Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, Shah N, Cai L, Efstathiou E, Logothetis C, et al, (2013) Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155: 1309-1322
40. Shi H, Hong A, Kong X, Koya RC, Song C, Moriceau G, Hugo W, Yu CC, Ng C, Chodon T, et al, (2014) A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition. Cancer Discov 4: 69-79
41. Leung AY, Man CH, Kwong YL, (2013) FLT3 inhibition: a moving and evolving target in acute myeloid leukaemia. Leukemia 27: 260-268
42. Wander SA, Levis MJ, Fathi AT, (2014) The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond. Ther Adv Hematol 5: 65-77
43. Corcoran RB, Ebi H, Turke AB, Coffee EM, Nishino M, Cogdill AP, Brown RD, Della Pelle P, Dias-Santagata D, Hung KE, et al, (2012) EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2: 227-235
44. Stegmeier F, Warmuth M, Sellers WR, Dorsch M, (2010) Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clin Pharmacol Ther 87: 543-552
45. Sharma SV, Settleman J, (2010) Exploiting the balance between life and death: targeted cancer therapy and "oncogenic shock". Biochem Pharmacol 80: 666-673
46. Sharma SV, Gajowniczek P, Way IP, Lee DY, Jiang J, Yuza Y, Classon M, Haber DA, Settleman J, (2006) A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell 10: 425-435
47. Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS, (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436: 720-724
48. Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, Gilbert C, Coffer P, Downward J, Evan G, (1997) Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 385: 544-548
49. Hermeking H, Eick D, (1994) Mediation of c-Myc-induced apoptosis by p53. Science 265: 2091-2093
50. Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC, (1992) Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119-128
51. Collado M, Serrano M, (2010) Senescence in tumours: evidence from mice and humans. Nat Rev Cancer 10: 51-57
52. Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, Rosen N, (2009) V600EBRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA 106: 4519-4524
53. Kim HJ, Bar-Sagi D, (2004) Modulation of signalling by Sprouty: a developing story. Nat Rev Mol Cell Biol 5: 441-450
54. Caunt CJ, Keyse SM, (2013) Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling. FEBS J 280: 489-504
55. Lito P, Pratilas CA, Joseph EW, Tadi M, Halilovic E, Zubrowski M, Huang A, Wong WL, Callahan MK, Merghoub T, et al, (2012) Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 22: 668-682
56. Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, 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
57. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R, (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483: 100-103
58. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, et al, (2014) Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 371: 1877-1888
59. Larkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, et al, (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371: 1867-1876
60. Lee HJ, Zhuang G, Cao Y, Du P, Kim HJ, Settleman J, (2014) Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell 26: 207-221
61. Asmussen J, Lasater EA, Tajon C, Oses-Prieto J, Jun YW, Taylor BS, Burlingame A, Craik CS, Shah NP, (2014) MEK-dependent negative feedback underlies BCR-ABL-mediated oncogene addiction. Cancer Discov 4: 200-215
62. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, et al, (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141: 69-80
63. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, et al, (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66: 1500-1508
64. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N, (2011) AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 19: 58-71
65. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, et al, (2011) Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19: 575-586
66. Raab SS, Meier FA, Zarbo RJ, Jensen DC, Geisinger KR, Booth CN, Krishnamurti U, Stone CH, Janosky JE, Grzybicki DM, (2006) The "Big Dog" effect: variability assessing the causes of error in diagnoses of patients with lung cancer. J Clin Oncol 24: 2808-2814
67. Blackhall F, Ranson M, Thatcher N, (2006) Where next for gefitinib in patients with lung cancer? Lancet Oncol 7: 499-507
68. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al, (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129-2139
69. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al, (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304: 1497-1500
70. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, et al, (2004) EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101: 13306-13311
71. Pao W, Girard N, (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12: 175-180
72. Huse JT, Phillips HS, Brennan CW, (2011) Molecular subclassification of diffuse gliomas: seeing order in the chaos. Glia 59: 1190-1199
73. Willyard C, (2013) 'Basket studies' will hold intricate data for cancer drug approvals. Nat Med 19: 655
74. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G, (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505: 495-501
75. Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM, Wang X, Gallo M, Garzia L, Zayne K, et al, (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506: 445-450
76. Giannakis M, Hodis E, Jasmine M, Yamauchi M, Rosenbluh J, Cibulskis K, Saksena G, Lawrence MS, Qian ZR, Nishihara R, et al, (2014) RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet 46: 1264-1266
77. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C, (2014) The landscape of kinase fusions in cancer. Nat Commun 5: 4846
78. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, et al, (2013) TERT promoter mutations in familial and sporadic melanoma. Science 339: 959-961
79. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA, (2013) Highly recurrent TERT promoter mutations in human melanoma. Science 339: 957-959
80. Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, et al, (2014) An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science 346: 1373-1377
81. Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74
82. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, et al, (2014) Defining functional DNA elements in the human genome. Proc Natl Acad Sci USA 111: 6131-6138
83. Nunes CB, Rocha RM, Buzelin MA, Balabram D, de Souza Foureaux F, Porto SS, Gobbi H, (2013) False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma. J Clin Pathol 66: 946-950
84. Little SE, Popov S, Jury A, Bax DA, Doey L, Al-Sarraj S, Jurgensmeier JM, Jones C, (2012) Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity. Cancer Res 72: 1614-1620
85. Snuderl M, Fazlollahi L, Le LP, Nitta M, Zhelyazkova BH, Davidson CJ, Akhavanfard S, Cahill DP, Aldape KD, Betensky RA, et al, (2011) Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 20: 810-817
86. Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, Ozawa T, Holland EC, Huse JT, Jhanwar S, et al, (2012) Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci USA 109: 3041-3046
87. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, et al, (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6: 224ra224
88. Zhang J, Fujimoto J, Zhang J, Wedge DC, Song X, Zhang J, Seth S, Chow CW, Cao Y, Gumbs C, et al, (2014) Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science 346: 256-259
89. Swanton C, (2012) Intratumor heterogeneity: evolution through space and time. Cancer Res 72: 4875-4882
90. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, et al, (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883-892
91. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, et al, (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481: 506-510
92. Brown-Glaberman U, Dayao Z, Royce M, (2014) HER2-targeted therapy for early-stage breast cancer: a comprehensive review. Oncology (Williston Park) 28: 281-289
93. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L, (2012) Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 9: 16-32
94. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, et al, (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355: 2408-2417
95. Rea D, Etienne G, Nicolini F, Cony-Makhoul P, Johnson-Ansah H, Legros L, Huguet F, Tulliez M, Gardembas M, Bouabdallah K, et al, (2012) First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia 26: 2254-2259
96. Palandri F, Castagnetti F, Testoni N, Luatti S, Marzocchi G, Bassi S, Breccia M, Alimena G, Pungolino E, Rege-Cambrin G, et al, (2008) Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. Haematologica 93: 1792-1796
97. Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, et al, (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497: 108-112
98. Garraway LA, Janne PA, (2012) Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov 2: 214-226
99. Balbas MD, Evans MJ, Hosfield DJ, Wongvipat J, Arora VK, Watson PA, Chen Y, Greene GL, Shen Y, Sawyers CL, (2013) Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife 2: e00499
100. Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, Moon M, Maneval EC, Chen I, Darimont B, et al, (2013) A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov 3: 1020-1029
101. Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, Yuan J, Kovats SG, Kim S, Cooke VG, et al, (2013) An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov 3: 1030-1043
102. Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ, Hatton C, Chopra R, Oberholzer PA, Karpova MB, et al, (2009) MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA 106: 20411-20416
103. Diehl P, Tedesco D, Chenchik A, (2014) Use of RNAi screens to uncover resistance mechanisms in cancer cells and identify synthetic lethal interactions. Drug Discov Today Technol 11: 11-18
104. Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, Frias RL, Gainor JF, Amzallag A, Greninger P, et al, (2014) Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 346: 1480-1486
105. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, et al, (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3: 75ra26
106. Yao Z, Fenoglio S, Gao DC, Camiolo M, Stiles B, Lindsted T, Schlederer M, Johns C, Altorki N, Mittal V, et al, (2010) TGF-beta IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancer. Proc Natl Acad Sci USA 107: 15535-15540
107. Suda K, Tomizawa K, Fujii M, Murakami H, Osada H, Maehara Y, Yatabe Y, Sekido Y, Mitsudomi T, (2011) Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib. J Thorac Oncol 6: 1152-1161
108. Terry S, Beltran H, (2014) The many faces of neuroendocrine differentiation in prostate cancer progression. Front Oncol 4: 60
109. Liegl B, Hornick JL, Antonescu CR, Corless CL, Fletcher CD, (2009) Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after tyrosine kinase inhibitor therapy: a novel form of tumor progression. Am J Surg Pathol 33: 218-226
110. Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA, Piris A, Frederick DT, Barzily-Rokni M, Straussman R, Haq R, et al, (2014) A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4: 816-827
111. Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, et al, (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 354: 2542-2551
112. Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, et al, (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362: 2251-2259
113. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, et al, (2013) A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 369: 1783-1796
114. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, et al, (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363: 809-819
115. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, et al, (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324: 787-790
116. Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, et al, (2014) Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 370: 1189-1197
117. Gadgeel SM, Gandhi L, Riely GJ, Chiappori AA, West HL, Azada MC, Morcos PN, Lee RM, Garcia L, Yu L, et al, (2014) Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol 15: 1119-1128
118. Fruman DA, Rommel C, (2014) PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13: 140-156
119. Dienstmann R, Rodon J, Serra V, Tabernero J, (2014) Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther 13: 1021-1031
120. Burtness B, Anadkat M, Basti S, Hughes M, Lacouture ME, McClure JS, Myskowski PL, Paul J, Perlis CS, Saltz L, et al, (2009) NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw 7 (Suppl 1): S5-S21; quiz S22-24
121. Herbst RS, LoRusso PM, Purdom M, Ward D, (2003) Dermatologic side effects associated with gefitinib therapy: clinical experience and management. Clin Lung Cancer 4: 366-369
122. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ, (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 105: 2070-2075
123. Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, et al, (2014) AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4: 1046-1061
124. Tjin Tham Sjin R, Lee K, Walter AO, Dubrovskiy A, Sheets M, Martin TS, Labenski MT, Zhu Z, Tester R, Karp R, et al, (2014) In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing. Mol Cancer Ther 13: 1468-1479
125. Zhang J, Adrian FJ, Jahnke W, Cowan-Jacob SW, Li AG, Iacob RE, Sim T, Powers J, Dierks C, Sun F, et al, (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 463: 501-506
126. Gilmartin AG, Bleam MR, Groy A, Moss KG, Minthorn EA, Kulkarni SG, Rominger CM, Erskine S, Fisher KE, Yang J, et al, (2011) GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 17: 989-1000
127. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS, et al, (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 9: 1956-1967
128. Ishii N, Harada N, Joseph EW, Ohara K, Miura T, Sakamoto H, Matsuda Y, Tomii Y, Tachibana-Kondo Y, Iikura H, et al, (2013) Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res 73: 4050-4060
129. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, et al, (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379: 633-640
130. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, et al, (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366: 109-119
131. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, et al, (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367: 1783-1791
132. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX, (2009) Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15: 429-440
133. Garner AP, Bialucha CU, Sprague ER, Garrett JT, Sheng Q, Li S, Sineshchekova O, Saxena P, Sutton CR, Chen D, et al, (2013) An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin. Cancer Res 73: 6024-6035
134. Britten CD, (2013) PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol 71: 1395-1409
135. Park KS, Raffeld M, Moon YW, Xi L, Bianco C, Pham T, Lee LC, Mitsudomi T, Yatabe Y, Okamoto I, et al, (2014) CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance. J Clin Invest 124: 3003-3015
136. Young RM, Staudt LM, (2014) Ibrutinib treatment of CLL: the cancer fights back. Cancer Cell 26: 11-13
137. Shah NP, Kasap C, Weier C, Balbas M, Nicoll JM, Bleickardt E, Nicaise C, Sawyers CL, (2008) Transient potent BCR-ABL inhibition is sufficient to commit chronic myeloid leukemia cells irreversibly to apoptosis. Cancer Cell 14: 485-493
138. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD, (2013) Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 494: 251-255
139. Fenton MA, Shuster TD, Fertig AM, Taplin ME, Kolvenbag G, Bubley GJ, Balk SP, (1997) Functional characterization of mutant androgen receptors from androgen-independent prostate cancer. Clin Cancer Res 3: 1383-1388
140. Riely GJ, Kris MG, Zhao B, Akhurst T, Milton DT, Moore E, Tyson L, Pao W, Rizvi NA, Schwartz LH, et al, (2007) Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res 13: 5150-5155
141. Schrodl K, von Schilling C, Tufman A, Huber RM, Gamarra F, (2014) Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK inhibitor in a patient with acquired crizotinib resistance. Respiration 88: 262-264
142. Browning ET, Weickhardt AJ, Camidge DR, (2013) Response to crizotinib rechallenge after initial progression and intervening chemotherapy in ALK lung cancer. J Thorac Oncol 8: e21
143. Foo J, Chmielecki J, Pao W, Michor F, (2012) Effects of pharmacokinetic processes and varied dosing schedules on the dynamics of acquired resistance to erlotinib in EGFR-mutant lung cancer. J Thorac Oncol 7: 1583-1593
144. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al, (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: 844-848
145. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, et al, (2005) An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435: 677-681
146. Weisberg E, Ray A, Barrett R, Nelson E, Christie AL, Porter D, Straub C, Zawel L, Daley JF, Lazo-Kallanian S, et al, (2010) Smac mimetics: implications for enhancement of targeted therapies in leukemia. Leukemia 24: 2100-2109
147. Gilmartin AG, Faitg TH, Richter M, Groy A, Seefeld MA, Darcy MG, Peng X, Federowicz K, Yang J, Zhang SY, et al, (2014) Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol 10: 181-187
148. DeLaBarre B, Hurov J, Cianchetta G, Murray S, Dang L, (2014) Action at a distance: allostery and the development of drugs to target cancer cell metabolism. Chem Biol 21: 1143-1161
149. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ, (2014) Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov 13: 828-851
150. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, et al, (2009) A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med 15: 750-756
151. Pop MS, Stransky N, Garvie CW, Theurillat JP, Hartman EC, Lewis TA, Zhong C, Culyba EK, Lin F, Daniels DS, et al, (2014) A small molecule that binds and inhibits the ETV1 transcription factor oncoprotein. Mol Cancer Ther 13: 1492-1502
152. Prinz F, Schlange T, Asadullah K, (2011) Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov 10: 712
153. Cheung HW, Cowley GS, Weir BA, Boehm JS, Rusin S, Scott JA, East A, Ali LD, Lizotte PH, Wong TC, et al, (2011) Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc Natl Acad Sci USA 108: 12372-12377
154. Hoffman GR, Rahal R, Buxton F, Xiang K, McAllister G, Frias E, Bagdasarian L, Huber J, Lindeman A, Chen D, et al, (2014) Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. Proc Natl Acad Sci USA 111: 3128-3133
155. Hsu PD, Lander ES, Zhang F, (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157: 1262-1278
156. Kaelin WG Jr, (2005) The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 5: 689-698
157. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, et al, (2012) The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483: 603-607
158. Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, et al, (2012) Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483: 570-575
159. Kim HS, Mendiratta S, Kim J, Pecot CV, Larsen JE, Zubovych I, Seo BY, Kim J, Eskiocak B, Chung H, et al, (2013) Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer. Cell 155: 552-566
160. Siolas D, Hannon GJ, (2013) Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res 73: 5315-5319
161. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, et al, (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159: 176-187
162. Liu X, Ory V, Chapman S, Yuan H, Albanese C, Kallakury B, Timofeeva OA, Nealon C, Dakic A, Simic V, et al, (2012) ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am J Pathol 180: 599-607
163. Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, et al, (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4: 568-580
164. Drake CG, Lipson EJ, Brahmer JR, (2014) Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol 11: 24-37
165. Barrett DM, Singh N, Porter DL, Grupp SA, June CH, (2014) Chimeric antigen receptor therapy for cancer. Annu Rev Med 65: 333-347
166. Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, et al, (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362: 2260-2270
167. Roumiantsev S, Shah NP, Gorre ME, Nicoll J, Brasher BB, Sawyers CL, Van Etten RA, (2002) Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc Natl Acad Sci USA 99: 10700-10705
168. Jabbour EJ, Cortes JE, Kantarjian HM, (2013) Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options. Clin Lymphoma Myeloma Leuk 13: 515-529
169. Traer E, Javidi-Sharifi N, Agarwal A, Dunlap J, English I, Martinez J, Tyner JW, Wong M, Druker BJ, (2014) Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations. Blood 123: 1516-1524
170. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, et al, (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472-480
171. Wang WL, Conley A, Reynoso D, Nolden L, Lazar AJ, George S, Trent JC, (2011) Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor. Cancer Chemother Pharmacol 67 (Suppl 1): S15-S24
172. Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, Vranckx H, Wasag B, Prenen H, Roesel J, 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
173. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, et al, (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364: 2507-2516
174. Shi H, Moriceau G, Kong X, Lee MK, Lee H, Koya RC, Ng C, Chodon T, Scolyer RA, Dahlman KB, et al, (2012) Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun 3: 724
175. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, et al, (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468: 973-977
176. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, Macconaill LE, Hahn WC, et al, (2011) Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol 29: 3085-3096
177. Lito P, Rosen N, Solit DB, (2013) Tumor adaptation and resistance to RAF inhibitors. Nat Med 19: 1401-1409
178. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al, (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362: 2380-2388
179. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, et al, (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11: 121-128
180. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al, (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13: 239-246
181. Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, et al, (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15: 213-222
182. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, et al, (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31: 3327-3334
183. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H, (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2: e73
184. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B, (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352: 786-792
185. Camidge DR, Pao W, Sequist LV, (2014) Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol 11: 473-481
186. Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, et al, (2011) Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med 3: 99ra86
187. Bardelli A, Siena S, (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28: 1254-1261
188. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, et al, (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368: 2385-2394
189. Katayama R, Friboulet L, Koike S, Lockerman EL, Khan TM, Gainor JF, Iafrate AJ, Takeuchi K, Taiji M, Okuno Y, et al, (2014) Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res 20: 5686-5696
190. Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, et al, (2012) Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med 4: 120ra117
191. Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman DJ, Heasley LE, Franklin WA, et al, (2012) Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 18: 1472-1482
192. Lovly CM, McDonald NT, Chen H, Ortiz-Cuaran S, Heukamp LC, Yan Y, Florin A, Ozretic L, Lim D, Wang L, et al, (2014) Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med 20: 1027-1034
193. Baselga J, Carbonell X, Castaneda-Soto NJ, Clemens M, Green M, Harvey V, Morales S, Barton C, Ghahramani P, (2005) Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 23: 2162-2171
194. Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, et al, (2009) Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol 10: 581-588
195. Rexer BN, Arteaga CL, (2012) Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog 17: 1-16
196. Chandarlapaty S, Sakr RA, Giri D, Patil S, Heguy A, Morrow M, Modi S, Norton L, Rosen N, Hudis C, et al, (2012) Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer. Clin Cancer Res 18: 6784-6791
197. Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, et al, (2014) Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 371: 1963-1971
198. Awad MM, Katayama R, McTigue M, Liu W, Deng YL, Brooun A, Friboulet L, Huang D, Falk MD, Timofeevski S, et al, (2013) Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med 368: 2395-2401
199. Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, et al, (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30: 134-141
200. Degos L, Dombret H, Chomienne C, Daniel MT, Miclea JM, Chastang C, Castaigne S, Fenaux P, (1995) All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood 85: 2643-2653
201. Gallagher RE, Moser BK, Racevskis J, Poire X, Bloomfield CD, Carroll AJ, Ketterling RP, Roulston D, Schachter-Tokarz E, Zhou DC, et al, (2012) Treatment-influenced associations of PML-RARalpha mutations, FLT3 mutations, and additional chromosome abnormalities in relapsed acute promyelocytic leukemia. Blood 120: 2098-2108
202. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, et al, (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367: 1187-1197
203. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, et al, (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371: 1028-1038
204. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, et al, (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381: 805-816
205. Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, et al, (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45: 1439-1445