Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer

Abstract

Cisplatin-based chemotherapy is a first-line treatment for muscle-invasive and metastatic urothelial cancer. Approximately 10% of bladder urothelial tumors have a somatic missense mutation in the nucleotide excision repair (NER) gene, ERCC2, which confers increased sensitivity to cisplatin-based chemotherapy. However, a significant subset of patients is ineligible to receive cisplatin-based therapy due to medical contraindications, and no NER-targeted approaches are available for platinum-ineligible or platinum-refractory ERCC2-mutant cases.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 18, 2020
Source ID
10.1158/1078-0432.ccr-20-3316

Entities

People

  • Amruta S. Samant
  • David B Solit
  • David J. Konieczkowski
  • David Liu
  • Dávid Szüts
  • Eliezer M. Van Allen
  • Elizabeth R. Plimack
  • Gopa Iyer
  • Helle Pappot
  • István Csabai
  • James A. Rodrigues
  • Jean H. Hoffman-censits
  • Jean-bernard Lazaro
  • Jonathan E Rosenberg
  • Judit Börcsök
  • Kasia M. Dillon
  • Kent W. Mouw
  • Mary-ellen Taplin
  • Miklos Diossy
  • Naresh Vasani
  • Orsolya Rusz
  • Raie Bekele
  • Rita Lozsa
  • Sizhi P. Gao
  • Sándor Spisák
  • Søren Brunak
  • Viktoria Tisza
  • Zoltán Szállási
  • Zoë J. Frazier
  • Zsófia Sztupinszki

Organizations

  • Boston Children's Hospital
  • Brigham and Women's Hospital
  • Dana–Farber Cancer Institute
  • Eötvös Loránd University
  • Fox Chase Cancer Center
  • Johns Hopkins University
  • Memorial Sloan Kettering Cancer Center
  • Novo Nordisk Fonden
  • Ohio State University
  • Semmelweis University
  • The Breast Cancer Research Foundation
  • The Velux Foundations
  • University of Copenhagen

Tags

Fields of Study

  • Medicine

Readers

  • Molecular Genetics
  • Oncology