PARP inhibition: targeting the Achilles' heel of DNA repair to treat germline and sporadic ovarian cancers.
Curr Opin Oncol
; 22(5): 473-80, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20485165
ABSTRACT
PURPOSE OF REVIEW Ovarian cancer remains the gynaecological malignancy with the highest mortality in the Western world. The strategy of identifying biologically distinct subgroups of ovarian cancer by means of clinical characteristics, histology and molecular profiling is an exciting prospect in personalizing and improving therapy for ovarian cancer. RECENT FINDINGS:
Preclinical recognition that BRCA1 and BRCA2-associated tumours are very sensitive to inhibition of poly-ADP ribose polymerase (PARP), a key molecule in DNA repair, led to ovarian cancer patients with germline BRCA1 and BRCA2 mutations being treated with the PARP inhibitor olaparib (AZD2281, KU-0059436; KuDOS/Astra-Zeneca). The initial trials of olaparib in this patient population demonstrated an impressive rate of clinical benefit. Furthermore, tumours from patients with sporadic ovarian cancer have been found to commonly have somatic BRCA1 and BRCA2 mutations or other defects in DNA repair, with the implication that PARP inhibition may also have a role in treating these patients.SUMMARY:
In this review, we discuss DNA repair mechanisms and strategies used to target them in oncology, our current experience with PARP inhibition in BRCA1 and BRCA2-mutation associated and sporadic ovarian cancer, as well as current issues in the clinical development of these agents.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Mutación de Línea Germinal
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Genes BRCA1
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Genes BRCA2
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Reparación del ADN
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Inhibidores de Poli(ADP-Ribosa) Polimerasas
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Curr Opin Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Reino Unido