PARPi, BRCA, and gaps: controversies and future research.
Trends Cancer
; 10(9): 857-869, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39004561
ABSTRACT
In recent years, various poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been approved for the treatment of several cancers to target the vulnerability of homologous recombination (HR) deficiency (e.g., due to BRCA1/2 dysfunction). In this review we analyze the ongoing debates and recent breakthroughs in the use of PARPis for BRCA1/2-deficient cancers, juxtaposing the 'double-strand break (DSB)' and 'single-stranded DNA (ssDNA) gap' models of synthetic lethality induced by PARPis. We spotlight the complexity of this interaction, highlighting emerging research on the role of DNA polymerase theta (POLθ) and ssDNA gaps in shaping therapy responses. We scrutinize the clinical ramifications of these findings, especially concerning PARPi efficacy and resistance mechanisms, underscoring the heterogeneity of BRCA-mutated tumors and the urgent need for advanced research to bridge the gap between laboratory models and patient outcomes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína BRCA1
/
Proteína BRCA2
/
Inhibidores de Poli(ADP-Ribosa) Polimerasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Trends Cancer
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos