OCT 22, 2020 12:25 PM SGT

The role of PARPis and HRD testing in advanced ovarian cancer

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Associate Consultant, National University Cancer Institute, Singapore
    Biography

      Dr Natalie Ngoi a medical oncologist at the National University Cancer Institute, Singapore (NCIS). Her primary clinical and research interests are in gynaecological cancers, genitourinary cancers, and precision oncology. Dr Ngoi graduated from the Yong Loo Lin School of Medicine, National University of Singapore with the degree of MBBS with Honours. She completed her Internal Medicine training at the National University Health System, Singapore and was awarded the Gordon Ransome Gold Medal in Internal Medicine. She undertook specialist training in Medical Oncology at the National University Cancer Institute, Singapore, and qualified as a Medical Oncologist in 2018. Dr Ngoi is currently an Associate Consultant in the gynaecological cancer and genitourinary cancer tumour groups at NCIS, and is an active member of the Gynecologic Cancer Group Singapore (GCGS) and Asia Pacific Gynaecologic Oncology Trials Group (APGOT). She is actively involved in the running of clinical trials at the Developmental Therapeutics Unit (NCIS), and is involved in ovarian cancer research at the Cancer Science Institute of Singapore (CSI).


    Abstract

    High grade serous ovarian cancer is characterized by genomic instability, with ~50% of advanced tumors harboring homologous recombination repair (HRR) pathway deficiency (HRD). HRD results in irreparable DNA damage and increased sensitivity to platinum chemotherapy, as well as increased susceptibility to poly-ADP ribose polymerase (PARP) inhibitors. PARPis are able to induce synthetic lethality in cells with HRD by binding to and trapping PARP1 and PARP2 to single-stranded DNA breaks, which generates double-stranded breaks. The lack of high-fidelity HRR in these cells leads to reliance on error-prone DNA repair pathways (e.g.: non-homologous end joining), further genomic instablity and cell death. The presence of HRD leads to detectable signature or genomic scar which can be scored by different tools. Available tools have computed the following: loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions to derive a summated HRD score. The HRD score has come to the fore as important individualised information in patients with advanced ovarian cancer, due to its correlation with response to maintenance PARPis in the first-line therapeutic setting. In this session, we discuss the role of PARPis in the treatment of advanced ovarian cancer, with particular focus on the use of HRD testing to better define optimal therapy for front-line treatment of these patients.

    Learning Objectives:
    1. To understand the role of PARPis in the treatment of advanced ovarian cancer
    2. Understanding biomarkers to select patients for PARPi therapy


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