Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing

Abstract

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Keywords: CRPC; androgen-deprivation therapy; drug repurposing; prostate cancer.

Figure 1

Clinical diagnosis, patient stratification, and treatment options for prostate cancer. Schematic of the clinical diagnosis and patient stratification for appropriate PCa treatment. Abbreviations: ADT: androgen deprivation therapy; Bx: biopsy; DRE: digital rectal examination; PSA: prostate specific antigen; RP: radical prostatectomy; RT: radiation therapy.

Figure 2

Drug repurposing in advanced prostate cancer. Using computational approaches and pre-clinical analyses, many Food and Drug Administration (FDA)-approved drugs could be identified and repurposed to treat patients with advanced prostate cancer. Abbreviations: FDA: U.S. Food and Drug Administration; NSAIDs: non-steroidal anti-inflammatory drugs.