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

被引：155

作者：

Merino, Delphine ^{[1
,2
]}

Whittle, James R. ^{[1
,2
,3
]}

Vaillant, Francois ^{[1
,2
]}

Serrano, Antonin ^{[1
,2
]}

Gong, Jia-Nan ^{[2
,4
]}

Giner, Goknur ^{[2
,5
]}

Maragno, Ana Leticia ^{[6
]}

Chanrion, Maia ^{[6
]}

Schneider, Emilie ^{[6
]}

Pal, Bhupinder ^{[1
,2
]}

Li, Xiang ^{[2
,7
]}

Dewson, Grant ^{[2
,7
]}

Grasel, Julius ^{[1
,2
]}

Liu, Kevin ^{[1
,2
]}

Lalaoui, Najoua ^{[2
,7
]}

Segal, David ^{[2
,4
]}

Herold, Marco J. ^{[2
,8
]}

Huang, David C. S. ^{[2
,4
]}

Smyth, Gordon K. ^{[5
,9
]}

Geneste, Olivier ^{[6
]}

Lessene, Guillaume ^{[2
,10
,11
]}

Visvader, Jane E. ^{[1
,2
]}

Lindeman, Geoffrey J. ^{[1
,3
,12
,13
,14
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, ACRF Stem Cells & Canc Div, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[3] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic 3000, Australia

[4] Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Parkville, Vic 3052, Australia

[5] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia

[6] Inst Rech Servier Oncol, R&D Unit, F-78290 Croissy Sur Seine, France

[7] Walter & Eliza Hall Inst Med Res, Cell Signalling & Cell Death Div, Parkville, Vic 3052, Australia

[8] Walter & Eliza Hall Inst Med Res, Mol Genet Canc Div, Parkville, Vic 3052, Australia

[9] Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia

[10] Walter & Eliza Hall Inst Med Res, Chem Biol Div, Parkville, Vic 3052, Australia

[11] Univ Melbourne, Dept Pharmacol & Therapeut, Parkville, Vic 3010, Australia

[12] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia

[13] Royal Melbourne Hosp, Parkville Familial Canc Ctr, Parkville, Vic 3050, Australia

[14] Peter MacCallum Canc Ctr, Parkville, Vic 3050, Australia

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2017年 / 9卷 / 401期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

SELECTIVE SMALL-MOLECULE; DIFFERENTIAL EXPRESSION ANALYSIS; TARGETING BCL2; BH3; MIMETICS; IN-VITRO; APOPTOSIS; CELLS; SENSITIVITY; LEUKEMIA; POTENT;

D O I：

10.1126/scitranslmed.aam7049

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.

引用

页数：10

共 67 条

[1] PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation [J].

Anderson, Grace R. ;

Wardell, Suzanne E. ;

Cakir, Merve ;

Crawford, Lorin ;

Leeds, Jim C. ;

Nussbaum, Daniel P. ;

Shankar, Pallavi S. ;

Soderquist, Ryan S. ;

Stein, Elizabeth M. ;

Tingley, Jennifer P. ;

Winter, Peter S. ;

Zieser-Misenheimer, Elizabeth K. ;

Alley, Holly M. ;

Yllanes, Alexander ;

Haney, Victoria ;

Blackwell, Kimberly L. ;

McCall, Shannon J. ;

McDonnell, Donald P. ;

Wood, Kris C. .

SCIENCE TRANSLATIONAL MEDICINE, 2016, 8 (369)

[2] An Inducible Lentiviral Guide RNA Platform Enables the Identification of Tumor-Essential Genes and Tumor-Promoting Mutations In Vivo [J].

Aubrey, Brandon J. ;

Kelly, Gemma L. ;

Kueh, Andrew J. ;

Brennan, Margs S. ;

O'Connor, Liam ;

Milla, Liz ;

Wilcox, Stephen ;

Tai, Lin ;

Strasser, Andreas ;

Herold, Marco J. .

CELL REPORTS, 2015, 10 (08) :1422-1432

[3] Molecular Profiling of the Residual Disease of Triple-Negative Breast Cancers after Neoadjuvant Chemotherapy Identifies Actionable Therapeutic Targets [J].

Balko, Justin M. ;

Giltnane, Jennifer M. ;

Wang, Kai ;

Schwarz, Luis J. ;

Young, Christian D. ;

Cook, Rebecca S. ;

Owens, Phillip ;

Sanders, Melinda E. ;

Kuba, Maria G. ;

Sanchez, Violeta ;

Kurupi, Richard ;

Moore, Preston D. ;

Pinto, Joseph A. ;

Doimi, Franco D. ;

Gomez, Henry ;

Horiuchi, Dai ;

Goga, Andrei ;

Lehmann, Brian D. ;

Bauer, Joshua A. ;

Pietenpol, Jennifer A. ;

Ross, Jeffrey S. ;

Palmer, Gary A. ;

Yelensky, Roman ;

Cronin, Maureen ;

Miller, Vincent A. ;

Stephens, Phillip J. ;

Arteaga, Carlos L. .

CANCER DISCOVERY, 2014, 4 (02) :232-245

[4] Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: therapeutic implications [J].

Bashari, Muhammad Hasan ;

Fan, Fengjuan ;

Vallet, Sonia ;

Sattler, Martin ;

Arn, Melissa ;

Luckner-Minden, Claudia ;

Schulze-Bergkamen, Henning ;

Zoernig, Inka ;

Marme, Frederik ;

Schneeweiss, Andreas ;

Cardone, Michael H. ;

Opferman, Joseph T. ;

Jaeger, Dirk ;

Podar, Klaus .

BREAST CANCER RESEARCH, 2016, 18

[5] Small molecule Mcl-1 inhibitors for the treatment of cancer [J].

Belmar, Johannes ;

Fesik, Stephen W. .

PHARMACOLOGY & THERAPEUTICS, 2015, 145 :76-84

[6] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[7] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[8]

Campone M., 2017, SCI TRANSL MED, V9

[9] c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1 [J].

Campone, Mario ;

Noel, Belinda ;

Couriaud, Cecile ;

Grau, Morgan ;

Guillemin, Yannis ;

Gautier, Fabien ;

Gouraud, Wilfried ;

Charbonnel, Catherine ;

Campion, Loic ;

Jezequel, Pascal ;

Braun, Frederique ;

Barre, Benjamin ;

Coqueret, Olivier ;

Barille-Nion, Sophie ;

Juin, Philippe .

MOLECULAR CANCER, 2011, 10

[10] The Bcl-2/Bcl-XL/Bcl-w Inhibitor, Navitoclax, Enhances the Activity of Chemotherapeutic Agents In Vitro and In Vivo [J].

Chen, Jun ;

Jin, Sha ;

Abraham, Vivek ;

Huang, Xiaoli ;

Liu, Bernard ;

Mitten, Michael J. ;

Nimmer, Paul ;

Lin, Xiaoyu ;

Smith, Morey ;

Shen, Yu ;

Shoemaker, Alexander R. ;

Tahir, Stephen K. ;

Zhang, Haichao ;

Ackler, Scott L. ;

Rosenberg, Saul H. ;

Maecker, Heather ;

Sampath, Deepak ;

Leverson, Joel D. ;

Tse, Chris ;

Elmore, Steven W. .

MOLECULAR CANCER THERAPEUTICS, 2011, 10 (12) :2340-2349

← 1 2 3 4 5 6 7 →