Targeting BCL-2 with the BH3 Mimetic ABT-199 in Estrogen Receptor-Positive Breast Cancer

被引：238

作者：

Vaillant, Francois ^{[1
,6
]}

Merino, Delphine ^{[1
,6
]}

Lee, Lily ^{[1
,6
]}

Breslin, Kelsey ^{[1
]}

Pal, Bhupinder ^{[1
,6
]}

Ritchie, Matthew E. ^{[2
,7
]}

Smyth, Gordon K. ^{[3
,7
]}

Christie, Michael ^{[4
,6
,10
]}

Phillipson, Louisa J. ^{[5
,6
]}

Burns, Christopher J. ^{[5
,6
]}

Mann, G. Bruce ^{[8
]}

Visvader, Jane E. ^{[1
,6
]}

Lindeman, Geoffrey J. ^{[1
,9
,11
,12
,13
]}

机构：

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

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

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

[4] Walter & Eliza Hall Inst Med Res, Syst Biol & Personalised Med Div, Parkville, Vic 3052, Australia

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

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

[7] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia

[8] Univ Melbourne, Dept Surg, Parkville, Vic 3010, Australia

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

[10] Royal Melbourne Hosp, Dept Anat Pathol, Parkville, Vic 3050, Australia

[11] Royal Melbourne Hosp, Dept Med Oncol, Parkville, Vic 3050, Australia

[12] Royal Melbourne Hosp, Breast Serv, Parkville, Vic 3050, Australia

[13] Royal Womens Hosp, Parkville, Vic 3050, Australia

来源：

CANCER CELL | 2013年 / 24卷 / 01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：

CHRONIC LYMPHOCYTIC-LEUKEMIA; SURVIVAL SIGNALS; CELL-DEATH; THERAPY; FAMILY; INHIBITOR; TUMORS; NAVITOCLAX; ABT-737; ACTIVATION;

D O I：

10.1016/j.ccr.2013.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The prosurvival protein BCL-2 is frequently overexpressed in estrogen receptor (ER)-positive breast cancer. We have generated ER-positive primary breast tumor xenografts that recapitulate the primary tumors and demonstrate that the BH3 mimetic ABT-737 markedly improves tumor response to the antiestrogen tamoxifen. Despite abundant BCL-XL expression, similar efficacy was observed with the BCL-2 selective inhibitor ABT-199, revealing that BCL-2 is a crucial target. Unexpectedly, BH3 mimetics were found to counteract the side effect of tamoxifen-induced endometrial hyperplasia. Moreover, BH3 mimetics synergized with phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors in eliciting apoptosis. Importantly, these two classes of inhibitor further enhanced tumor response in combination therapy with tamoxifen. Collectively, our findings provide a rationale for the clinical evaluation of BH3 mimetics in therapy for breast cancer.

引用

页码：120 / 129

页数：10

共 39 条

[21] THE PROLIFERATION OF NORMAL HUMAN BREAST-TISSUE IMPLANTED INTO ATHYMIC NUDE-MICE IS STIMULATED BY ESTROGEN BUT NOT PROGESTERONE
LAIDLAW, IJ
CLARKE, RB
HOWELL, A
OWEN, AWMC
POTTEN, CS
ANDERSON, E
[J]. ENDOCRINOLOGY, 1995, 136 (01) : 164 - 171
[22] Tamoxifen and ICI 182,780 increase Bcl-2 levels and inhibit growth of breast carcinoma cells by modulating PI3K/AKT, ERK and IGF-1R pathways independent of ERα
Lam, Le
Hu, Xiuying
Aktary, Zackie
Andrews, David W.
Pasdar, Manijeh
[J]. BREAST CANCER RESEARCH AND TREATMENT, 2009, 118 (03) : 605 - 621
[23] Patient-derived breast tumor xenografts facilitating personalized cancer therapy
Landis, Melissa D.
Lehmann, Brian D.
Pietenpol, Jennifer A.
Chang, Jenny C.
[J]. BREAST CANCER RESEARCH, 2013, 15 (01)
[24] Lindeman GJ, 2013, BREAST CANCER MANAG, V2, P1
[25] Programmed anuclear cell death delimits platelet life span
Mason, Kylie D.
Carpinelli, Marina R.
Fletcher, Jamie I.
Collinge, Janelle E.
Hilton, Adrienne A.
Ellis, Sarah
Kelly, Priscilla N.
Ekert, Paul G.
Metcalf, Donald
Roberts, Andrew W.
Huang, David C. S.
Kile, Benjamin T.
[J]. CELL, 2007, 128 (06) : 1173 - 1186
[26] Bcl-2, Bcl-xL, and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
Merino, Delphine
Khaw, Seong L.
Glaser, Stefan P.
Anderson, Daniel J.
Belmont, Lisa D.
Wong, Chihunt
Yue, Peng
Robati, Mikara
Phipson, Belinda
Fairlie, Walter D.
Lee, Erinna F.
Campbell, Kirsteen J.
Vandenberg, Cassandra J.
Cory, Suzanne
Roberts, Andrew W.
Ludlam, Mary J. C.
Huang, David C. S.
Bouillet, Philippe
[J]. BLOOD, 2012, 119 (24) : 5807 - 5816
[27] Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737
Moore, Victoria Del Gaizo
Brown, Jennifer R.
Certo, Michael
Love, Tara M.
Novina, Carl D.
Letai, Anthony
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (01) : 112 - 121
[28] Inhibition of PI3K/mTOR Leads to Adaptive Resistance in Matrix-Attached Cancer Cells
Muranen, Taru
Selfors, Laura M.
Worster, Devin T.
Iwanicki, Marcin P.
Song, Loling
Morales, Fabiana C.
Gao, Sizhen
Mills, Gordon B.
Brugge, Joan S.
[J]. CANCER CELL, 2012, 21 (02) : 227 - 239
[29] Aberrant Expression of Apoptosis-Related Molecules in Endometriosis: A Possible Mechanism Underlying the Pathogenesis of Endometriosis
Nasu, Kaei
Nishida, Masakazu
Kawano, Yukie
Tsuno, Akitoshi
Abe, Wakana
Yuge, Akitoshi
Takai, Noriyuki
Narahara, Hisashi
[J]. REPRODUCTIVE SCIENCES, 2011, 18 (03) : 206 - 218
[30] Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737
Oakes, Samantha R.
Vaillant, Francois
Lim, Elgene
Lee, Lily
Breslin, Kelsey
Feleppa, Frank
Deb, Siddhartha
Ritchie, Matthew E.
Takano, Elena
Ward, Teresa
Fox, Stephen B.
Generali, Daniele
Smyth, Gordon K.
Strasser, Andreas
Huang, David C. S.
Visvader, Jane E.
Lindeman, Geoffrey J.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (08) : 2766 - 2771

← 1 2 3 4 →