Implications of Bcl-2 and its interplay with other molecules and signaling pathways in prostate cancer progression

Among several genetic alterations involved in the progression of prostate cancer, B cell lymphoma gene number 2 (BCL-2) is an important target molecule in the progression of androgen-independent prostate cancer (AIPC) after androgen ablation or castration. Nevertheless, the molecular mechanism of BCL-2 in prostate cancer progression remains elusive and controversial. In the current review, we discuss the critical role of BCL-2 in the carcinogenesis of prostate cancer with experimental evidences on the BCL-2 molecular networks in AIPC and androgen-dependent prostate cancer (ADPC) and subsequently suggest perspective research targeting BCL-2. Areas covered: This review focused on the molecular implications of BCL-2 in association with other molecules and signaling pathways involved in the progression and carcinogenesis of prostate cancer. Expert opinion: BCL-2 plays a pivotal role in the progression of AIPC than in ADPC since androgen represses BCL-2. BCL-2 acts as a pro-survival molecule in association with androgen-related signaling in the progression of ADPC, while BCL-2 upregulation, PTEN loss, PI3K/AKT phosphorylation and receptor tyrosine kinase (RTK) activation are primarily involved in AIPC. To identify more effective prostate cancer therapy, further mechanistic studies are required with BCL-2 inhibitors in AIPC and ADPC, considering a multi-target therapy against BCL-2 and its related signaling.

Expert opinion on therapeutic targets. 2017 Aug 17 [Epub ahead of print]

Ju-Ha Kim, Hyemin Lee, Eun Ah Shin, Dong Hee Kim, Jhin Baek Choi, Sung-Hoon Kim

a Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine, Kyung Hee University , Seoul 130-701 , South Korea., b Department of East West Medical Science, Graduate School of East West Medical Science , Kyung Hee University , Yongin , 446-701 , South Korea.