Prostate cancer (PCa) will account for about 1460 000 cases and 396 000 deaths in 2022, making it the second most frequent cancer among males globally (Bray et al., 2024). This disparity between cancer incidence and lethality has led to widespread scrutiny of disease management, especially those with indolent disease. Due to these facts, finding a biomarker that will help determine which patient has clinically significant PCa is critical.

The prostate-specific antigen (PSA) test and digital rectal exam (DRE) are usually recommended to detect PCa. PSA level above (>4 ng/mL) is considered as a possible indicator of PCa (Hall et al., 2017). Although PSA testing has significantly reduced mortality rates and enabled early detection of PCa, its specificity is weak. Several non-cancerous diseases such as infection, inflammation, and benign prostatic hyperplasia (BPH) may also be responsible for elevated PSA levels, and therefore, using PSA as a sole biomarker for PCa diagnosis has led to a high rate of false positive results (Potosky et al., 2001). Furthermore, a patient with a high PSA level may suffer more adverse consequences from treatment for indolent cancer than beneficial outcomes. On the other hand, some cases with normal PSA levels have also shown clinically significant diseases. This could result in the underdiagnosis of clinically significant PCa, increasing mortality (Cuvillier and Malavaud, 2011; Velonas et al., 2013). In this direction, several adjunctive biomarker tests, including protein, nucleic acid and metabolite biomarkers are being developed in liquid biopsy methods to predict the risk of clinically significant PCa with minimally invasive procedures and avoid “overdiagnosed” and “overtreated” patients.

For patients with recurrent or metastatic PCa, ADT is the treatment of choice. Unfortunately, several patients do not respond to ADT, and metastatic cancer converts from castration sensitive to CRPC (Karantanos et al., 2013). Many treatment options are currently available nowadays for the treatment of CRPC, including next-generation androgen signaling inhibitors (enzalutamide, abiraterone), chemotherapy (docetaxel and cabazitaxel), radiotherapy (radium-223) and immunotherapy (sipuleucel-T) (Nuhn et al., 2019). Nonetheless, primary and acquired resistance to these drugs is more common. Serum PSA is not an adequate marker for the evaluation of treatment response, and thus, biomarkers predicting treatment resistance are needed. Genetic alterations are strongly associated with CRPC and underline the heterogeneous characteristics of tumors. Therefore, for the successful treatment of PCa and to develop precision medicine, it is essential to monitor the treatment response and resistance using suitable biomarkers. The use of poly ADP-ribose polymerase (PARP) and AKT pathway inhibitors for patients with BRCA1 and phosphatase and tensin homolog (PTEN) alterations, respectively, are promising (Mateo et al., 2015). Given the potent oncogenic activity of certain noncoding RNA (ncRNA) and their prostate-specific expression, it can be used as both biomarkers and therapeutic targets for PCa. Therefore, characterizing and utilizing biomarkers that can be used as therapeutic targets and predict disease survival or treatment response will provide a noble approach to the effective execution of personalized therapies for the benefit of PCa patients.

This review mainly focused on different types of biomarkers and summarized how effectively these biomarkers have been used in diagnostic, predictive, prognostic, and therapeutic purposes for treating PCa. We also provide an overview of the key delivery approaches that can improve drug stability and minimize adverse effects.