G Protein-Coupled Receptors in Prostate Cancer: Pathophysiological Implications and Potential for Innovative Therapeutics

Prostate cancer (PCa) is one of the leading causes of cancer-related death among men worldwide. Considerable efforts have been devoted to developing more effective therapeutic strategies for PCa, particularly for metastatic castration-resistant prostate cancer (mCRPC), wherein resistance to androgen-receptor pathway inhibition remains a major clinical challenge. G protein-coupled receptors (GPCRs), the largest family of cell surface signaling receptors, regulate numerous physiological and pathological processes and represent major therapeutic targets across multiple diseases, including cancer. In PCa, hormone- and inflammation-related GPCRs have emerged as key regulators of tumor initiation, progression, therapeutic resistance, and metastasis. Accordingly, understanding the contribution of GPCR signaling to PCa biology may reveal novel opportunities for therapeutic intervention, particularly in mCRPC. In this review, we summarize the current knowledge on the expression and function of GPCRs in PCa development, progression, and metastasis, highlighting their potential as therapeutic targets and discussing opportunities for drug development, combination therapies, and drug repurposing.