39PD - Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in GALAXY-1 (NCT01348126), a randomized phase 2b study o...

Date 27 March 2014
Event ELCC 2014
Session Poster Discussion 1
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Dean Fennell
Citation Journal of Thoracic Oncology (2014) 9 (Supplement 9): S7-S52. 10.1097/JTO.0000000000000131
Authors D. Fennell1, J. Shaw2, I. El-Hariry3, V.M. Vukovic3, V. Reichert4, L.M. Martins5
  • 1Thoracic Medical Oncology, University Hospitals of Leicester Leicester Royal Infirmary, LE1 9HN - Leicester/UK
  • 2Cancer Studies And Molecular Medicine, University of Leicester, LE2 7 LX - Leicester/UK
  • 3Clinical, Synta Pharmaceuticals, 02421 - Lexington/US
  • 4Translational Research, Synta Pharmaceuticals, 02421 - Lexington/US
  • 5Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester/UK

Abstract

Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins critical to NSCLC growth and aggressiveness, can lead to cancer cell death. Ganetespib (G) is a 2nd generation Hsp90 inhibitor (Hsp90i) that has shown single agent clinical activity in patients with tumors harboring ALK, KRAS, HER2, and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals allowing detection of somatic mutations by deep sequencing. The aim of this work was to determine the mutational spectrum of patients enrolled into the GALAXY-1 trial using this liquid biopsy strategy.