TY - JOUR
T1 - Beyond breast and ovarian cancers
T2 - PARP inhibitors for BRCA mutation-associated and BRCA-like solid tumors
AU - O'Sullivan, Ciara C.
AU - Moon, Dominic H.
AU - Kohn, Elise C.
AU - Lee, Jung Min
PY - 2014
Y1 - 2014
N2 - Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers.
AB - Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers.
KW - BRCA mutation
KW - BRCA-like
KW - DNA damage repair pathway
KW - Poly(ADP-ribose) polymerase inhibitors
KW - solid tumors
UR - http://www.scopus.com/inward/record.url?scp=84898020932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898020932&partnerID=8YFLogxK
U2 - 10.3389/fonc.2014.00042
DO - 10.3389/fonc.2014.00042
M3 - Review article
C2 - 24616882
AN - SCOPUS:84898020932
SN - 2234-943X
VL - 4 MAR
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - Article 42
ER -