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Abstract 2185: Identification of novel compounds that preferentially kill repair deficient cells using high-throughput screening

Abstract 2185: Identification of novel compounds that preferentially kill repair deficient cells using high-throughput screening

Authors :
Jane S. Merkel
Peter M. Glazer
Laura Abriola
Elizabeth Peterson-Roth
Source :
Cancer Research. 70:2185-2185
Publication Year :
2010
Publisher :
American Association for Cancer Research (AACR), 2010.

Abstract

Loss of functional DNA repair pathways is a common occurrence in cancer cells and discovery of novel drugs that selectively kill repair deficient tumors cells could identify new cancer therapies. In this work we describe the use of high-throughput screening to determine chemicals that sensitize cells deficient in the fanconi anemia protein, FANCD2. Cell growth of human fibroblasts proficient (PD20+D2) and deficient (PD20) for FANCD2 were screened using two libraries containing over 1000 bioactive compounds and kinase inhibitors. The cells were treated with compounds continuously for 3 days and cell growth was assessed using a luciferase-based assay measuring ATP levels. The initial screen identified numerous compounds inducing differential survival in cells with and without FANCD2 and follow-up testing will be required to confirm these potential hits. However, it is promising that, in addition to novel compounds, several crosslinking agents, including mitomycinC, which are known to sensitize fanconi anemia cells to cell death are among the positive hits. Our results validate chemical screening as a tool to discover potential new cancer therapies targeting repair deficient cells lines. In addition, other than their role in crosslink repair, there is still not much known about the fanconi anemia protein family and the discovery of novel compounds involved in FANCD2 dependent cell survival could lead to the discovery of new functions of this protein family. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2185.

Details

ISSN :
15387445 and 00085472
Volume :
70
Database :
OpenAIRE
Journal :
Cancer Research
Accession number :
edsair.doi...........2dfe9fc5a8941f0311c3bb8ee52423c1
Full Text :
https://doi.org/10.1158/1538-7445.am10-2185