Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Cancers

Albert Jang¹  PedroC. Barata¹  Oliver Sartor¹  ChanningJ. Paller² 

[1] Deming Department of Medicine, Hematology-Oncology Section, Tulane University School of Medicine, New Orleans, LA 70112, USA;The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;

关键词: metastatic castration-resistant prostate cancer;    PARP inhibitor;    olaparib;    rucaparib;    niraparib;    talazoparib;   

DOI  :  10.3390/cancers12113467

来源: DOAJ

【 摘 要 】

Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes. Poly (ADP-ribose) polymerase (PARP) inhibitors take advantage of HRR deficiency to kill tumor cells based on the concept of synthetic lethality. Several PARP inhibitors (PARPis) have been successful in various malignancies with HRR gene mutations including BRCA1/2, especially in breast cancer and ovarian cancer. More recently, olaparib and rucaparib were approved for mCRPC refractory to novel hormonal therapies, and other PARPis will likely follow. This article highlights the mechanism of action of PARPis at the cellular level, the preclinical data regarding a proposed mechanism of action and the effectiveness of PARPis in cancer cell lines and animal models. The article expands on the clinical development of PARPis in mCRPC, discusses potential biomarkers that may predict successful tumor control, and summarizes present and future clinical research on PARPis in the metastatic disease landscape.

【 授权许可】

Unknown