Announcements

Seminar In Medicine, 22.11.2018, Dr. İrem Durmaz Şahin

Author: KUSOM
Time: 14:00
Location: MED 176

KOÇ UNIVERSITY

SCHOOL OF MEDICINE

 
SEMINAR IN MEDICINE
Thursday, November 22th,
 2018

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Speaker         : Dr. İrem Durmaz Şahin, Lund University, Department of 
Division of Oncology and Pathology

Title               : Homologous Recombination Deficiency and Novel Targeted Treatment Strategies In Ovarian Cancer

Time              : 14.00 (Refreshments will be served at 13:45)

Place              : MED 176

TelePresence   : AH 5th floor Chief Medical Officer / KUH 9th floor Meeting Room

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HOMOLOGOUS RECOMBINATION DEFICIENCY AND NOVEL TARGETED TREATMENT STRATEGIES IN OVARIAN CANCER

High-grade serous ovarian cancer (HGSOC) is the predominant and most lethal histological subtype of epithelial ovarian cancer. FDA has approved the PARP inhibitors for the maintenance treatment of platinum-sensitive, recurrent HGSOC; however, drug resistance limits their efficacy. The overall aim of this project was to enhance our understanding of this disease in terms of heterogeneity and treatment response. We investigated the prevalence of homologous recombination repair deficiency (HRD) beyond mutations in BRCA1/2, and the association with response to PARP inhibition with the ultimate goal of defining a larger group of patients eligible for PARP inhibition. With the goal of developing personalized targeted therapies, novel combinatorial treatment strategies were investigated. Combination treatment with the c-met inhibitor and a PARP inhibitor was strongly synergistic and induced cell cycle arrest via activation of the ATM/CHK pathway and inhibition of Akt and ERK pathways, all contributing to induction of apoptosis. Combination treatments with the standard-of-care chemotherapeutic carboplatin and a PARP inhibitor was less efficacious. Importantly, findings from cell lines were recapitulated in human primary cancer cells derived from ascites fluid. These results indicate the potential benefit of combining crizotinib and PARP inhibitors to enhance the activity of PARP inhibitors as a new therapeutic strategy in HGSOC.