LAUSR

Simple Summary Prostate cancer treatment has improved over the last 20 years; despite this, approximately 33,000 men died from the disease in the United States in 2020. In view of this, new treatment options are urgently needed for advanced prostate cancer. Eradicating cancer cells by triggering apoptosis (a form of cell death) is an attractive strategy, and a novel class of drugs, called BH3 mimetics, have been designed to do this. They have been shown to work for blood cancers and may also have a role in solid cancers. Herein, we discuss cell death, focusing on the intrinsic apoptosis pathway, and consider how BH3 mimetics may be used to help treat prostate cancer. Abstract Despite major improvements in the management of advanced prostate cancer over the last 20 years, the disease remains invariably fatal, and new effective therapies are required. The development of novel hormonal agents and taxane chemotherapy has improved outcomes, although primary and acquired resistance remains problematic. Inducing cancer cell death via apoptosis has long been an attractive goal in the treatment of cancer. Apoptosis, a form of regulated cell death, is a highly controlled process, split into two main pathways (intrinsic and extrinsic), and is stimulated by a multitude of factors, including cellular and genotoxic stress. Numerous therapeutic strategies targeting the intrinsic apoptosis pathway are in clinical development, and BH3 mimetics have shown promising efficacy for hematological malignancies. Utilizing these agents for solid malignancies has proved more challenging, though efforts are ongoing. Molecular characterization and the development of predictive biomarkers is likely to be critical for patient selection, by identifying tumors with a vulnerability in the intrinsic apoptosis pathway. This review provides an up-to-date overview of cell death and apoptosis, specifically focusing on the intrinsic pathway. It summarizes the latest approaches for targeting the intrinsic apoptosis pathway with BH3 mimetics and discusses how these strategies may be leveraged to treat prostate cancer.