The Role of BCL-2 Proteins in the Development of Castration-resistant Prostate Cancer and Emerging Therapeutic Strategies

被引:4
作者
Soliman, Luke [1 ]
De Souza, Andre [1 ,2 ,3 ]
Srinivasan, Praveen [1 ]
Danish, Matthew [1 ,2 ]
Bertone, Paul [1 ,2 ,3 ]
El-Deiry, Wafik S. [1 ,2 ,3 ,4 ]
Carneiro, Benedito A. [1 ,2 ,3 ]
机构
[1] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA
[2] Lifespan Canc Inst, Div Hematol Oncol, Providence, RI USA
[3] Brown Univ, Canc Ctr, Providence, RI 02912 USA
[4] Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA
来源
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS | 2021年 / 44卷 / 07期
关键词
prostate cancer; androgen resistance; BCL-2; castration-resistant prostate cancer; inhibitor; ANDROGEN-INDEPENDENT GROWTH; RANDOMIZED PHASE-II; ANTISENSE OLIGONUCLEOTIDE; RADIATION-THERAPY; OBLIMERSEN SODIUM; EXPRESSION; CELLS; FAMILY; INHIBITION; DOCETAXEL;
D O I
10.1097/COC.0000000000000829
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The development of androgen resistance in advanced prostate cancer remains a challenging clinical problem. Because androgen deprivation therapy constitutes the backbone of first-line treatments for metastatic prostate cancer, the phenotypic switch from an androgen-dependent to an androgen-independent growth state limits the treatment options for these patients. This critical change from an androgen-dependent to an androgen-independent growth state can be regulated by the B-cell lymphoma gene 2 (BCL-2) family of apoptotic proteins. While the roles of BCL-2 protein family members in the carcinogenesis of prostate cancer have been well-studied, emerging data also delineates their modulation of disease progression to castration-resistant prostate cancer (CRPC). Over the past 2 decades, investigators have sought to describe the mechanisms that underpin this development at the molecular level, yet no recent literature has consolidated these findings in a dedicated review. As new classes of BCL-2 family inhibitors are finding indications for other cancer types, it is time to evaluate how such agents might find stable footing for the treatment of CRPC. Several trials to date have investigated BCL-2 inhibitors as therapeutic agents for CRPC. These therapies include selective BCL-2 inhibitors, pan-BCL-2 inhibitors, and novel inhibitors of MCL-1 and BCL-X-L. This review details the research regarding the role of BCL-2 family members in the pathogenesis of prostate cancer and contextualizes these findings within the contemporary landscape of prostate cancer treatment.
引用
收藏
页码:374 / 382
页数:9
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