PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers.
Expert Opin Investig Drugs
; 31(6): 607-631, 2022 Jun.
Article
in En
| MEDLINE
| ID: mdl-35435784
ABSTRACT
INTRODUCTION:
Poly (ADP-ribose) polymerase inhibitors (PARPis) are an exciting class of agents that have shown efficacy, particularly for BRCA-mutant triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC). However, most patients who receive PARPi as their standard of care therapy inevitably develop resistance and this underscores the need to identify additional targets that can circumvent such resistance. Combination treatment strategies have been developed in preclinical and clinical studies to address the challenges of efficacy and resistance. AREAS COVERED This review examines completed or ongoing clinical trials of PARPi mono- and combination therapies. PARPi monotherapy in HER2 negative breast (HR+ and TNBC subtypes) and ovarian cancer is a focal point. The authors propose potential strategies that might overcome resistance to PARPi and discuss key questions and future directions. EXPERT OPINION While the advent of PARPis has significantly improved the treatment of tumors with defects in DNA damage and repair pathways, careful patient selection will be essential to enhance these treatments. The identification of molecular biomarkers to predict disease response and progression is an endeavor.Key words
Clinical trial; DNA damage repair (DDR); combination therapy; drug resistance; fluzoparib; germline BRCA-mutation; high-grade serous ovarian cancer (HGSOC); homologous recombination deficiency (HRD); immunotherapy; niraparib; olaparib; pamiparib; poly (ADP-ribose) polymerase (PARP) inhibitor; preclinical study; rucaparib; somatic BRCA-mutation; talazoparib; triple-negative breast cancer (TNBC); veliparib
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Triple Negative Breast Neoplasms
Limits:
Female
/
Humans
Language:
En
Journal:
Expert Opin Investig Drugs
Journal subject:
TERAPIA POR MEDICAMENTOS
Year:
2022
Document type:
Article