Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

Science Translational Medicine

Volumn 9, Issue 401, 2017, Pages

  Merino, Delphine ^a,b   Whittle, James R ^a,b,c   Vaillant, François ^a,b   Serrano, Antonin ^a,b   Gong, Jia Nan ^a,b   Giner, Goknur ^a,b   Maragno, Ana Leticia ^d   Chanrion, Maïa ^d   Schneider, Emilie ^d   Pal, Bhupinder ^a,b   Li, Xiang ^a,b   Dewson, Grant ^a,b   Gräsel, Julius ^a,b   Liu, Kevin ^a,b   Lalaoui, Najoua ^a,b   Segal, David ^a,b   Herold, Marco J ^a,b   Huang, David C S ^a,b   Smyth, Gordon K ^a,e   Geneste, Olivier ^d   Lessene, Guillaume ^a,b   Visvader, Jane E ^a,b   Lindeman, Geoffrey J ^a,b,c,f   more..

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c PETER MACCALLUM CANCER CENTRE   (Australia)

^d INSTITUT DE RECHERCHES SERVIER   (France)

^e UNIVERSITY OF MELBOURNE   (Australia)

^f ROYAL MELBOURNE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

DOCETAXEL; LAPATINIB; PROTEIN INHIBITOR; S 63845; TRASTUZUMAB; UNCLASSIFIED DRUG; EPIDERMAL GROWTH FACTOR RECEPTOR 2; PROTEIN BAK; PROTEIN BCL X; PROTEIN MCL 1; PYRIMIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; S63845; TAXOID; THIOPHENE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CANCER RESISTANCE; COHORT ANALYSIS; CONTROLLED STUDY; CRISPR CAS SYSTEM; CRISPR CAS9 SYSTEM; DRUG POTENTIATION; EMBRYO; EPIDERMAL GROWTH FACTOR RECEPTOR 2 AMPLIFIED BREAST CANCER; HUMAN; HUMAN CELL; HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 AMPLIFIED BREAST CANCER; IN VITRO STUDY; IN VIVO STUDY; LIMIT OF QUANTITATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; TREATMENT RESPONSE; TRIPLE NEGATIVE BREAST CANCER; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST TUMOR; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; FEMALE; GENE AMPLIFICATION; GENETICS; METABOLISM; PATHOLOGY; SURVIVAL ANALYSIS; TREATMENT OUTCOME; TUMOR CELL LINE;

ANIMALS; BCL-2 HOMOLOGOUS ANTAGONIST-KILLER PROTEIN; BCL-X PROTEIN; BREAST NEOPLASMS; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; FEMALE; GENE AMPLIFICATION; HUMANS; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PYRIMIDINES; QUINAZOLINES; RECEPTOR, ERBB-2; SURVIVAL ANALYSIS; TAXOIDS; THIOPHENES; TRASTUZUMAB; TREATMENT OUTCOME; TRIPLE NEGATIVE BREAST NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85026642556     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aam7049     Document Type: Article

References (66)

1. C. Curtis, S. P. Shah, S.-F. Chin, G. Turashvili, O. M. Rueda, M. J. Dunning, D. Speed, A. G. Lynch, S. Samarajiwa, Y. Yuan, S. Graf, G. Ha, G. Haffari, A. Bashashati, R. Russell, S. McKinney, M. Group, A. Langerød, A. Green, E. Provenzano, G. Wishart, S. Pinder, P. Watson, F. Markowetz, L. Murphy, I. Ellis, A. Purushotham, A.-L. Børresen-Dale, J. D. Brenton, S. Tavaré, C. Caldas, S. Aparicio, The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346-352 (2012).
2. A. Prat, C. M. Perou, Deconstructing the molecular portraits of breast cancer. Mol. Oncol. 5, 5-23 (2011).
3. K. D. Mason, M. R. Carpinelli, J. I. Fletcher, J. E. Collinge, A. A. Hilton, S. Ellis, P. N. Kelly, P. G. Ekert, D. Metcalf, A. W. Roberts, D. C. S. Huang, B. T. Kile, Programmed anuclear cell death delimits platelet life span. Cell 128, 1173-1186 (2007).
4. T. Oltersdorf, S. W. Elmore, A. R. Shoemaker, R. C. Armstrong, D. J. Augeri, B. A. Belli, M. Bruncko, T. L. Deckwerth, J. Dinges, P. J. Hajduk, M. K. Joseph, S. Kitada, S. J. Korsmeyer, A. R. Kunzer, A. Letai, C. Li, M. J. Mitten, D. G. Nettesheim, S. Ng, P. M. Nimmer, J. M. O'Connor, A. Oleksijew, A. M. Petros, J. C. Reed, W. Shen, S. K. Tahir, C. B. Thompson, K. J. Tomaselli, B. Wang, M. D. Wendt, H. Zhang, S. W. Fesik, S. H. Rosenberg, An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435, 677-681 (2005).
5. A. W. Roberts, M. S. Davids, J. M. Pagel, B. S. Kahl, S. D. Puvvada, J. F. Gerecitano, T. J. Kipps, M. A. Anderson, J. R. Brown, L. Gressick, S. Wong, M. Dunbar, M. Zhu, M. B. Desai, E. Cerri, S. Heitner Enschede, R. A. Humerickhouse, W. G. Wierda, J. F. Seymour, Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374, 311-322 (2016).
6. A. J. Souers, J. D. Leverson, E. R. Boghaert, S. L. Ackler, N. D. Catron, J. Chen, B. D. Dayton, H. Ding, S. H. Enschede, W. J. Fairbrother, D. C. S. Huang, S. G. Hymowitz, S. Jin, S. L. Khaw, P. J. Kovar, L. T. Lam, J. Lee, H. L. Maecker, K. C. Marsh, K. D. Mason, M. J. Mitten, P. M. Nimmer, A. Oleksijew, C. H. Park, C. M. Park, D. C. Phillips, A. W. Roberts, D. Sampath, J. F. Seymour, M. L. Smith, G. M. Sullivan, S. K. Tahir, C. Tse, M. D. Wendt, Y. Xiao, J. C. Xue, H. Zhang, R. A. Humerickhouse, S. H. Rosenberg, S. W. Elmore, ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19, 202-208 (2013).
7. A. W. Roberts, D. C. S. Huang, Targeting BCL2 with BH3 mimetics: Basic science and clinical application of venetoclax in chronic lymphocytic leukemia and related B cell malignancies. Clin. Pharmacol. Ther. 101, 89-98 (2017).
8. D. Merino, S. W. Lok, J. E. Visvader, G. J. Lindeman, Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. Oncogene 35, 1877-1887 (2016).
9. S.-J. Dawson, N. Makretsov, F. M. Blows, K. E. Driver, E. Provenzano, J. Le Quesne, L. Baglietto, G. Severi, G. G. Giles, C. A. McLean, G. Callagy, A. R. Green, I. Ellis, K. Gelmon, G. Turashvili, S. Leung, S. Aparicio, D. Huntsman, C. Caldas, P. Pharoah, BCL2 in breast cancer: A favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br. J. Cancer 103, 668-675 (2010).
10. F. Vaillant, D. Merino, L. Lee, K. Breslin, B. Pal, M. E. Ritchie, G. K. Smyth, M. Christie, L. J. Phillipson, C. J. Burns, G. B. Mann, J. E. Visvader, G. J. Lindeman, Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell 24, 120-129 (2013).
11. R. Beroukhim, C. H. Mermel, D. Porter, G. Wei, S. Raychaudhuri, J. Donovan, J. Barretina, J. S. Boehm, J. Dobson, M. Urashima, K. T. Mc Henry, R. M. Pinchback, A. H. Ligon, Y. J. Cho, L. Haery, H. Greulich, M. Reich, W. Winckler, M. S. Lawrence, B. A. Weir, K. E. Tanaka, D. Y. Chiang, A. J. Bass, A. Loo, C. Hoffman, J. Prensner, T. Liefeld, Q. Gao, D. Yecies, S. Signoretti, E. Maher, F. J. Kaye, H. Sasaki, J. E. Tepper, J. A. Fletcher, J. Tabernero, J. Baselga, M. S. Tsao, F. Demichelis, M. A. Rubin, P. A. Janne, M. J. Daly, C. Nucera, R. L. Levine, B. L. Ebert, S. Gabriel, A. K. Rustgi, C. R. Antonescu, M. Ladanyi, A. Letai, L. A. Garraway, M. Loda, D. G. Beer, L. D. True, A. Okamoto, S. L. Pomeroy, S. Singer, T. R. Golub, E. S. Lander, G. Getz, W. R. Sellers, M. Meyerson, The landscape of somatic copy-number alteration across human cancers. Nature 463, 899-905 (2010).
12. S.-H. Wei, K. Dong, F. Lin, X. Wang, B. Li, J.-j. Shen, Q. Zhang, R. Wang, H.-Z. Zhang, Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell. Cancer Chemother. Pharmacol. 62, 1055-1064 (2008).
13. I. E. Wertz, S. Kusam, C. Lam, T. Okamoto, W. Sandoval, D. J. Anderson, E. Helgason, J. A. Ernst, M. Eby, J. Liu, L. D. Belmont, J. S. Kaminker, K. M. O'Rourke, K. Pujara, P. B. Kohli, A. R. Johnson, M. L. Chiu, J. R. Lill, P. K. Jackson, W. J. Fairbrother, S. Seshagiri, M. J. C. Ludlam, K. G. Leong, E. C. Dueber, H. Maecker, D. C. S. Huang, V. M. Dixit, Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature 471, 110-114 (2011).
14. W. J. Placzek, J. Wei, S. Kitada, D. Zhai, J. C. Reed, M. Pellecchia, A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy. Cell Death Dis. 6, e40 (2010).
15. A. I. J. Young, A. M. K. Law, L. Castillo, S. Chong, H. D. Cullen, M. Koehler, S. Herzog, T. Brummer, E. F. Lee, W. D. Fairlie, M. C. Lucas, D. Herrmann, A. Allam, P. Timpson, D. N. Watkins, E. K. Millar, S. A. O'Toole, D. Gallego-Ortega, C. J. Ormandy, S. R. Oakes, MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib. Breast Cancer Res. 18, 125 (2016).
16. Q. Ding, X. He, W. Xia, J.-M. Hsu, C.-T. Chen, L. Y. Li, D.-F. Lee, J. Y. Yang, X. Xie, J.-C. Liu, M.-C. Hung, Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3β activity and associates with poor prognosis in human breast cancer. Cancer Res. 67, 4564-4571 (2007).
17. C. M. Goodwin, O. W. Rossanese, E. T. Olejniczak, S. W. Fesik, Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer. Cell Death Differ. 22, 2098-2106 (2015).
18. Y. Xiao, P. Nimmer, G. S. Sheppard, M. Bruncko, P. Hessler, X. Lu, L. Roberts-Rapp, W. N. Pappano, S. W. Elmore, A. J. Souers, J. D. Leverson, D. C. Phillips, MCL-1 is a key determinant of breast cancer cell survival: Validation of MCL-1 dependency utilizing a highly selective small molecule inhibitor. Mol. Cancer Ther. 14, 1837-1847 (2015).
19. M. H. Bashari, F. Fan, S. Vallet, M. Sattler, M. Arn, C. Luckner-Minden, H. Schulze-Bergkamen, I. Zörnig, F. Marme, A. Schneeweiss, M. H. Cardone, J. T. Opferman, D. Jäger, K. Podar, Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: Therapeutic implications. Breast Cancer Res. 18, 26 (2016).
20. E. S. Henson, X. Hu, S. B. Gibson, Herceptin sensitizes ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1 expression. Clin. Cancer Res. 12, 845-853 (2006).
21. C. Mitchell, A. Yacoub, H. Hossein, A. P. Martin, M. D. Bareford, P. Eulitt, C. Yang, K. P. Nephew, P. Dent, Inhibition of MCL-1 in breast cancer cells promotes cell death in vitro and in vivo. Cancer Biol. Ther. 10, 903-917 (2010).
22. J. M. Balko, J. M. Giltnane, K. Wang, L. J. Schwarz, C. D. Young, R. S. Cook, P. Owens, M. E. Sanders, M. G. Kuba, V. Sánchez, R. Kurupi, P. D. Moore, J. A. Pinto, F. D. Doimi, H. Gomez, D. Horiuchi, A. Goga, B. D. Lehmann, J. A. Bauer, J. A. Pietenpol, J. S. Ross, G. A. Palmer, R. Yelensky, M. Cronin, V. A. Miller, P. J. Stephens, C. L. Arteaga, Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov. 4, 232-245 (2014).
23. P. E. Czabotar, E. F. Lee, M. F. van Delft, C. L. Day, B. J. Smith, D. C. S. Huang, W. D. Fairlie, M. G. Hinds, P. M. Colman, Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc. Natl. Acad. Sci. U.S.A. 104, 6217-6222 (2007).
24. N. A. Cohen, M. L. Stewart, E. Gavathiotis, J. L. Tepper, S. R. Bruekner, B. Koss, J. T. Opferman, L. D. Walensky, A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chem. Biol. 19, 1175-1186 (2012).
25. A. Friberg, D. Vigil, B. Zhao, R. N. Daniels, J. P. Burke, P. M. Garcia-Barrantes, D. Camper, B. A. Chauder, T. Lee, E. T. Olejniczak, S. W. Fesik, Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design. J. Med. Chem. 56, 15-30 (2013).
26. T. Lee, Z. Bian, B. Zhao, L. J. Hogdal, J. L. Sensintaffar, C. M. Goodwin, J. Belmar, S. Shaw, J. C. Tarr, N. Veerasamy, S. M. Matulis, B. Koss, M. A. Fischer, A. L. Arnold, D. V. Camper, C. F. Browning, O. W. Rossanese, A. Budhraja, J. Opferman, L. H. Boise, M. R. Savona, A. Letai, E. T. Olejniczak, S. W. Fesik, Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Lett. 591, 240-251 (2016).
27. J. D. Leverson, H. Zhang, J. Chen, S. K. Tahir, D. C. Phillips, J. Xue, P. Nimmer, S. Jin, M. Smith, Y. Xiao, P. Kovar, A. Tanaka, M. Bruncko, G. S. Sheppard, L. Wang, S. Gierke, L. Kategaya, D. J. Anderson, C. Wong, J. Eastham-Anderson, M. J. Ludlam, D. Sampath, W. J. Fairbrother, I. Wertz, S. H. Rosenberg, C. Tse, S. W. Elmore, A. J. Souers, Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 6, e1590 (2015).
28. M. L. Stewart, E. Fire, A. E. Keating, L. D. Walensky, The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol. 6, 595-601 (2010).
29. A. Kotschy, Z. Szlavik, J. Murray, J. Davidson, A. L. Maragno, G. Le Toumelin-Braizat, M. Chanrion, G. L. Kelly, J. N. Gong, D. M. Moujalled, A. Bruno, M. Csekei, A. Paczal, Z. B. Szabo, S. Sipos, G. Radics, A. Proszenyak, B. Balint, L. Ondi, G. Blasko, A. Robertson, A. Surgenor, P. Dokurno, I. Chen, N. Matassova, J. Smith, C. Pedder, C. Graham, A. Studeny, G. Lysiak-Auvity, A. M. Girard, F. Gravé, D. Segal, C. D. Riffkin, G. Pomilio, L. C. A. Galbraith, B. J. Aubrey, M. S. Brennan, M. J. Herold, C. Chang, G. Guasconi, N. Cauquil, F. Melchiore, N. Guigal-Stephan, B. Lockhart, F. Colland, J. A. Hickman, A. W. Roberts, D. C. S. Huang, A. H. Wei, A. Strasser, G. Lessene, O. Geneste, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature 538, 477-482 (2016).
30. A. Letai, S63845, an MCL-1 selective BH3 mimetic: Another arrow in our quiver. Cancer Cell 30, 834-835 (2016).
31. The Cancer Genome Atlas Network, Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 (2012).
32. G. Lessene, P. E. Czabotar, B. E. Sleebs, K. Zobel, K. N. Lowes, J. M. Adams, J. B. Baell, P. M. Colman, K. Deshayes, W. J. Fairbrother, J. A. Flygare, P. Gibbons, W. J. A. Kersten, S. Kulasegaram, R. M. Moss, J. P. Parisot, B. J. Smith, I. P. Street, H. Yang, D. C. S. Huang, K. G. Watson, Structure-guided design of a selective BCL-XL inhibitor. Nat. Chem. Biol. 9, 390-397 (2013).
33. N. E. Sanjana, O. Shalem, F. Zhang, Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783-784 (2014).
34. H. Dai, H. Ding, X. W. Meng, K. L. Peterson, P. A. Schneider, J. E. Karp, S. H. Kaufmann, Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells. Genes Dev. 29, 2140-2152 (2015).
35. N. Cruickshanks, H. A. Hamed, M. D. Bareford, A. Poklepovic, P. B. Fisher, S. Grant, P. Dent, Lapatinib and obatoclax kill tumor cells through blockade of ERBB1/3/4 and through inhibition of BCL-XL and MCL-1. Mol. Pharmacol. 81, 748-758 (2012).
36. M. Campone, B. Noël, C. Couriaud, M. Grau, Y. Guillemin, F. Gautier, W. Gouraud, C. Charbonnel, L. Campion, P. Jézéquel, F. Braun, B. Barré, O. Coqueret, S. Barillé-Nion, P. Juin, c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1. Mol. Cancer 10, 110 (2011).
37. Q. Ding, X. He, J.-M. Hsu, W. Xia, C.-T. Chen, L.-Y. Li, D.-F. Lee, J.-C. Liu, Q. Zhong, X. Wang, M.-C. Hung, Degradation of Mcl-1 by β-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol. Cell. Biol. 27, 4006-4017 (2007).
38. R. M. Perciavalle, J. T. Opferman, Delving deeper: MCL-1's contributions to normal and cancer biology. Trends Cell Biol. 23, 22-29 (2013).
39. N. Y. Fu, A. C. Rios, B. Pal, R. Soetanto, A. T. L. Lun, K. Liu, T. Beck, S. A. Best, F. Vaillant, P. Bouillet, A. Strasser, T. Preiss, G. K. Smyth, G. J. Lindeman, J. E. Visvader, EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival. Nat. Cell Biol. 17, 365-375 (2015).
40. S. R. Oakes, F. Vaillant, E. Lim, L. Lee, K. Breslin, F. Feleppa, S. Deb, M. E. Ritchie, E. Takano, T. Ward, S. B. Fox, D. Generali, G. K. Smyth, A. Strasser, D. C. S. Huang, J. E. Visvader, G. J. Lindeman, Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737. Proc. Natl. Acad. Sci. U.S.A. 109, 2766-2771 (2012).
41. K. A. Sarosiek, A. Letai, Directly targeting the mitochondrial pathway of apoptosis for cancer therapy with BH3 mimetics: Recent successes, current challenges and future promise. FEBS J. 283, 3523-3533 (2016).
42. L/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol. Cancer Ther. 10, 2340-2349 (2011).
43. J. D. Leverson, D. C. Phillips, M. J. Mitten, E. R. Boghaert, D. Diaz, S. K. Tahir, L. D. Belmont, P. Nimmer, Y. Xiao, X. M. Ma, K. N. Lowes, P. Kovar, J. Chen, S. Jin, M. Smith, J. Xue, H. Zhang, A. Oleksijew, T. J. Magoc, K. S. Vaidya, D. H. Albert, J. M. Tarrant, N. La, L. Wang, Z.-F. Tao, M. D. Wendt, D. Sampath, S. H. Rosenberg, C. Tse, D. C. S. Huang, W. J. Fairbrother, S. W. Elmore, A. J. Souers, Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci. Transl. Med. 7, 279ra240 (2015).
44. G. R. Anderson, S. E. Wardell, M. Cakir, L. Crawford, J. C. Leeds, D. P. Nussbaum, P. S. Shankar, R. S. Soderquist, E. M. Stein, J. P. Tingley, P. S. Winter, E. K. Zieser-Misenheimer, H. M. Alley, A. Yllanes, V. Haney, K. L. Blackwell, S. J. McCall, D. P. McDonnell, K. C. Wood, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation. Sci. Transl. Med. 8, 369ra175 (2016).
45. J. L. Rinkenberger, S. Horning, B. Klocke, K. Roth, S. J. Korsmeyer, Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev. 14, 23-27 (2000).
46. A. R. D. Delbridge, S. Grabow, A. Strasser, D. L. Vaux, Thirty years of BCL-2: Translating cell death discoveries into novel cancer therapies. Nat. Rev. Cancer 16, 99-109 (2016).
47. X. Wang, M. Bathina, J. Lynch, B. Koss, C. Calabrese, S. Frase, J. D. Schuetz, J. E. Rehg, J. T. Opferman, Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes Dev. 27, 1351-1364 (2013).
48. R. M. Perciavalle, D. P. Stewart, B. Koss, J. Lynch, S. Milasta, M. Bathina, J. Temirov, M. M. Cleland, S. Pelletier, J. D. Schuetz, R. J. Youle, D. R. Green, J. T. Opferman, Antiapoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nat. Cell Biol. 14, 575-583 (2012).
49. J. Belmar, S. W. Fesik, Small molecule Mcl-1 inhibitors for the treatment of cancer. Pharmacol. Ther. 145, 76-84 (2015).
50. F. Llambi, T. Moldoveanu, S. W. G. Tait, L. Bouchier-Hayes, J. Temirov, L. L. McCormick, C. P. Dillon, D. R. Green, A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol. Cell 44, 517-531 (2011).
51. D. Yecies, N. E. Carlson, J. Deng, A. Letai, Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood 115, 3304-3313 (2010).
52. M. F. van Delft, A. H. Wei, K. D. Mason, C. J. Vandenberg, L. Chen, P. E. Czabotar, S. N. Willis, C. L. Scott, C. L. Day, S. Cory, J. M. Adams, A. W. Roberts, D. C. S. Huang, The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10, 389-399 (2006).
53. G. Dontu, W. M. Abdallah, J. M. Foley, K. W. Jackson, M. F. Clarke, M. J. Kawamura, M. S. Wicha, In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17, 1253-1270 (2003).
54. M. N. Prichard, L. E. Prichard, W. A. Baguley, M. R. Nassiri, C. Shipman Jr., Threedimensional analysis of the synergistic cytotoxicity of ganciclovir and zidovudine. Antimicrob. Agents Chemother. 35, 1060-1065 (1991).
55. L. A. O'Reilly, C. Print, G. Hausmann, K. Moriishi, S. Cory, D. C. S. Huang, A. Strasser, Tissue expression and subcellular localization of the pro-survival molecule Bcl-w. Cell Death Differ. 8, 486-494 (2001).
56. B. J. Aubrey, G. L. Kelly, A. J. Kueh, M. S. Brennan, L. O'Connor, L. Milla, S. Wilcox, L. Tai, A. Strasser, M. J. Herold, An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo. Cell Rep. 10, 1422-1432 (2015).
57. Z. Xu, P. P. Sharp, Y. Yao, D. Segal, C. H. Ang, S. L. Khaw, B. J. Aubrey, J. Gong, G. L. Kelly, M. J. Herold, A. Strasser, A. W. Roberts, W. S. Alexander, C. J. Burns, D. C. S. Huang, S. P. Glaser, BET inhibition represses miR17-92 to drive BIM-initiated apoptosis of normal and transformed hematopoietic cells. Leukemia 30, 1531-1541 (2016).
58. M. D. Robinson, A. Oshlack, A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).
59. M. D. Robinson, D. J. McCarthy, G. K. Smyth, edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140 (2010).
60. Y. Benjamini, Y. Hochberg, Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Methodol. 57, 289-300 (1995).
61. Y. Liao, G. K. Smyth, W. Shi, The Subread aligner: Fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 41, e108 (2013).
62. Y. Liao, G. K. Smyth, W. Shi, featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923-930 (2014).
63. M. E. Ritchie, B. Phipson, D. Wu, Y. Hu, C. W. Law, W. Shi, G. K. Smyth, limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
64. B. Phipson, S. Lee, I. J. Majewski, W. S. Alexander, G. K. Smyth, Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression. Ann. Appl. Stat. 10, 946-963 (2016).
65. C. W. Law, Y. Chen, W. Shi, G. K. Smyth, voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).
66. G. K. Smyth, J. Michaud, H. S. Scott, Use of within-array replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21, 2067-2075 (2005).