Prostate cancer is the main cause of mortality among males the global level and hold its 4th position as per Globocan data. Multiple treatment options are available for patients with low‑grade prostate cancer and metastatic disease. Therapeutic biomarkers hold significant potential for identifying treatment responses either prior to commencing any therapy or following therapy. For example, the high expression of androgen receptor splice variant 7 is a well‑established driver of resistance to both androgen‑axis‑targeted therapies and 223Ra treatments in prostate cancer. Additionally, prostate‑specific membrane antigen (PSMA) exhibits a significantly increased expression in prostate adenocarcinoma in comparison to normal tissue. Elevated PSMA levels are strongly associated with tumor aggressiveness. Despite the potential of biomarkers, identifying clinically actionable biomarkers remains a notable challenge due to several factors. A key obstacle is the heterogeneity of cancer cells, which can exhibit diverse molecular profiles even within the same tumor. Other challenges include the development of reliable assays, the lack of standardized methodologies for biomarker measurement and validation, sample availability, the high development cost, limited accessibility in low resource settings and stringent requirements for regulatory approval. Furthermore, the variability in tumor behavior necessitates tailored therapeutic strategies, as a one‑size‑fits‑all approach is unlikely to be effective. Therefore, it is necessary to address the challenges associated with the currently available biomarkers in order for risk stratification and treatment efficacy to be personalized. The present review discusses recent advancements in the field of therapeutic biomarkers against prostate cancer to assess the therapeutic response, progress of therapy, associated challenges and considerations to overcome the challenges.

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