Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer.

Autor: Bouberhan S; Department of Hematology/Medical Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Hematology/Medical Oncology, Harvard Medical School, Boston, MA 02115, USA., Philp L; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA 02115, USA., Hill S; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Al-Alem LF; Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA 02115, USA., Rueda B; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 May 11; Vol. 12 (5). Date of Electronic Publication: 2020 May 11.
DOI: 10.3390/cancers12051206
Abstrakt: High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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