Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

“Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.”


Collaborative Effort Aims to Find Strategies to Preempt Resistance to Prostate Cancer Therapies


The ‘Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer’ 3-year project aims to understand how prostate tumors become resistant to two newer drugs for prostate cancer that target the androgen receptor pathway—enzalutamide and abiraterone acetate. Continue reading…


Autophagy Can Modulate Responses to Treatments in Castration-Resistant Prostate Cancer Patients

Dr. Christopher P. Evans examines how autophagy, a relatively recently appreciated mechanism in cell and tumor biology, can regulate responses to prostate cancer treatments including chemotherapy and anti-androgen therapy in castrate-resistant prostate cancer.