Bcl-2 is a negative prognostic indicator in prostate cancer, implicated in the development of androgen independence and treatment resistance, and is overexpressed in hormone-refractory prostate cancer (HRPC).
Bcl-2 and Bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02.
BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3).
Bcl-2 overexpression is commonly associated with various cancers including breast cancer, prostate cancer, B-cell lymphomas and colorectal adenocarcinomas etc.
A natural BH3-mimetic, small-molecule inhibitor of Bcl-2, (-)-gossypol, shows promise in ongoing phase II and III clinical trials for human prostate cancer.
According to the above-mentioned four pathways, the following markers of response were identified: transcription of the oncogene TMPRSS2:ERG, translation of Aurora-A, coding of β1C integrin gene, translation of Ki-67, expression of nerve growth factors TrkA and p75NGFR, anti-angiogenic activity and micro-vessel density were involved into suppression of proliferation; mRNA transcription of bcl-2, expression of cleaved caspase-3 and translation of insulin growth factor binding protein 3, into induction of apoptosis; expression of IL-7 gene, programmed death-ligand 1, and increase of intra-prostatic T-cell population were related to alteration of immune response; finally, expression of heat shock protein 27 and de-differentiation of PCa to neuroendocrine cells, influenced the onset of hormonal refractoriness.
Antisense oligonucleotides (oligos) have been employed against prostate cancer models targeting growth-regulatory proteins, and at least one oligo (against bcl-2) has reached clinical trial.
BAG-1L (Bcl-2-associated anthanogene 1) has been found to interact with androgen receptor (AR), and has been suggested to be involved in the development of prostate cancer.
Bcl-xL, a novel member of anti-apoptotic Bcl-2 family that play important roles in regulating cell survival and apoptosis, is frequently overexpressed in various kinds of human cancers, including prostatic carcinoma.
Because inherent cellular radioresistance plays a critical role in the failure of radiotherapy, in this study, we investigated whether there is a correlation between the ratio of two apoptosis regulators, bcl-2 (apoptosis suppressor) and bax (apoptosis inducer) in prostatic tumors and the clinical response to radiotherapy in patients with localized prostate cancer.
By efficiently destroying the intracellular bcl-2 mRNA, one might be able to make the prostate cancer cell responsive again to conventional apoptotic stimuli such as androgen withdrawal.