Abstract
Inhibiting the androgen receptor (AR) is the standard of care to treat metastatic or recurrent prostate cancer. While treatment is initially effective, the cancer almost always develops resistance and progresses into a lethal castrate-resistant prostate cancer (CRPC). Notably, extensive clinical evidence has shown that the AR remains the main driver of growth and proliferation in CRPC patients. Yet, we increasingly find that conventional antiandrogens cannot effectively inhibit these resistant tumors. There is therefore a pressing need for new therapeutics that work through a novel mechanism of action to overcome drug resistance. This chapter describes our understanding of CRPC progression, highlights the underlying mechanisms of resistance, and provides an overview of the current preclinical and clinical small molecule AR inhibitors.
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