Current update on toll-like receptors and prostate cancer: a decade of progress and emerging insights

Prostate cancer remains the most common cancer and the second leading cause of cancer-related mortality among men in the United States. Despite advances in therapy, relapses and progression of disease continue to pose major clinical challenges, underscoring the need for innovative strategies. A decade ago, we reviewed the emerging evidence linking Toll-like receptors (TLRs), a family of innate immune sensors, to prostate cancer initiation and progression. Since then, substantial advances have deepened our understanding of TLR biology in prostate cancer, revealing their role in either promoting tumor growth or activating anti-tumor immunity depending on cellular context and signaling pathways. Recent studies have expanded knowledge of TLR expression on both immune and tumor cells, identified key endogenous ligands driving chronic inflammation, and uncovered microRNA-mediated regulation of TLR signaling. Moreover, new insights into TLR polymorphisms and their potential association with cancer risk, as well as preclinical and clinical progress in TLR-targeted immunotherapies, highlight both opportunities and challenges in translating TLR biology into therapeutic applications. In this review, we update the field by summarizing the latest discoveries, evaluating the complexities of TLR signaling in prostate cancer, and discussing how this evolving knowledge may inform future biomarker development and immunotherapeutic strategies.