Metastatic Castration Resistant Prostate Cancer (mCRPC) is a major unmet medical need due to its widespread occurrence and incurable status. The mCRPC market is expect to grow to more than $10B by 2020.
Current standard of care for advanced prostate cancer is androgen-deprivation therapy (ADT), and upon failure, patients are administered secondary ADT with androgen receptor (AR) signaling antagonists such as enzalutamide and abiraterone. While most patients display an initial response to these agents, eventually all become resistant via various mechanisms that often result in constitutive AR signaling including mutations of the AR, and the generation of AR splice variants that bypass the ligand binding domain. Other mechanisms of resistance to AR antagonists include up-regulation of the glucocorticoid receptor (GR), and partial to complete loss of AR signaling through neuroendocrine differentiation. A recent presentation highlighted the efficacy of ZEN-3694 in various models of AR-signaling positive or negative mCRPC that are resistant to current therapies.
Disease Progression in Prostate Cancer