Abstract
Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments.
Highlights
Prostate cancer (PC) is a major cause of morbidity and mortality in men
Rucaparib has been approved for use in combination with androgen receptors to guide therapy and chemotherapy based on paclitaxel harmful BRCA mutations in patients with metastatic castration-resistant prostate cancer (mCRPC)
Olaparib has been shown to be effective in prostate cancer (PC) patients who were no longer responding to standard treatments and who had defects in DNA repairs genes
Summary
Prostate cancer (PC) is a major cause of morbidity and mortality in men. It is the most common noncutaneous cancer in men, with an estimated 1.6 million cases and 0.36 million deaths annually [1]. BRCA mutations, this marked the first clinical acceptance of the feasibility of PARP1 as an anti-tumor target and the SL theory Another PARPi, rucaparib, received accelerated approval in the United States in December 2016 for advanced ovarian cancer with BRCA gene mutations and two or more chemotherapy treatments. Based on the successful application of PARPi in BRCA-deficient breast cancer and ovarian cancer, PARPis have become a new research focus, with many clinical trials for the treatment of metastatic PC (mPC) showing good efficacy by the mechanism of synthetic lethality [26,27] These inhibitors are associated with problems such as drug resistance. (2) the application of PARPis in the precision treatment of castration-resistant prostate cancer; (3) the current progress of clinical research; (4) the mechanism of PARPis’ drug resistance; (5) strategies for combination treatments and aims to provide insights into the clinical treatment of PC
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