TY - JOUR
T1 - PARP inhibitors in metastatic prostate cancer
T2 - Evidence to date
AU - Nizialek, Emily
AU - Antonarakis, Emmanuel S.
N1 - Funding Information:
Dr Antonarakis is partially funded by NIH grant P30 CA006973 and DOD grant W81XWH-16-PCRP-CCRSA.
PY - 2020
Y1 - 2020
N2 - Poly (ADP-ribose) polymerase inhibitors (PARPi) are a unique class of antineoplas-tic agents that function by inducing synthetic lethality. Synthetic lethality occurs when PARPi and either another agent or an underlying genetic alteration together lead to overwhelming DNA damage and ultimately cell death. PARPi first showed promise as a cancer therapy in patients with BRCA1/2 mutations and have become part of standard treatment for breast and ovarian cancer. In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). While both agents are approved for tumors with BRCA1/2 alterations, for olaparib the indication is also expanded to patients with 12 other homologous recombination deficiency (HRD) gene alterations including ATM and PALB2. PARPi differ in their pharmacokinetics and pharmacodynamics, and additional studies are being conducted with niraparib, veliparib, and talazoparib in prostate cancer. While PARPi are fairly well tolerated, common toxicities include hematologic (anemia/thrombocyto-penia) and gastrointestinal effects (nausea/vomiting). Ongoing studies are being conducted combining PARPi with other agents in patients with and without HRD alterations. Early data are promising for the combination of PARPi with second-generation antiandrogens and with immunotherapy. As additional trials are developed and reported, the hope is that the patient population who may benefit from PARPi will continue to expand.
AB - Poly (ADP-ribose) polymerase inhibitors (PARPi) are a unique class of antineoplas-tic agents that function by inducing synthetic lethality. Synthetic lethality occurs when PARPi and either another agent or an underlying genetic alteration together lead to overwhelming DNA damage and ultimately cell death. PARPi first showed promise as a cancer therapy in patients with BRCA1/2 mutations and have become part of standard treatment for breast and ovarian cancer. In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). While both agents are approved for tumors with BRCA1/2 alterations, for olaparib the indication is also expanded to patients with 12 other homologous recombination deficiency (HRD) gene alterations including ATM and PALB2. PARPi differ in their pharmacokinetics and pharmacodynamics, and additional studies are being conducted with niraparib, veliparib, and talazoparib in prostate cancer. While PARPi are fairly well tolerated, common toxicities include hematologic (anemia/thrombocyto-penia) and gastrointestinal effects (nausea/vomiting). Ongoing studies are being conducted combining PARPi with other agents in patients with and without HRD alterations. Early data are promising for the combination of PARPi with second-generation antiandrogens and with immunotherapy. As additional trials are developed and reported, the hope is that the patient population who may benefit from PARPi will continue to expand.
KW - Homologous recombination
KW - PARP inhibitor
KW - Prostate cancer
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U2 - 10.2147/CMAR.S227033
DO - 10.2147/CMAR.S227033
M3 - Review article
C2 - 32982407
AN - SCOPUS:85090650514
VL - 12
SP - 8105
EP - 8114
JO - Cancer Management and Research
JF - Cancer Management and Research
SN - 1179-1322
ER -