Accession Number:

ADA621643

Title:

Defining New Treatment Approaches for KRAS-Mutant Lung Cancer

Descriptive Note:

Annual rept. 30 Sep 2013-29 Sep 2014

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

2014-10-01

Pagination or Media Count:

7.0

Abstract:

Lung cancer is a deadly malignancy. The most commonly mutated oncogene we know is KRAS. We do not have a drug to inhibit KRAS , and medicinal chemistry approaches have exhausted leads. We need a new approach to find new ways to inhibit this oncogene. Objective To identify cellular cofactors required for KRAS G12D -driven NSCLC. Specific Aim 1 To identify gene products specifically essential for KRAS-driven NSCLC, we will perform a shRNA screen of thousands of mouse genes, looking for essentiality in multiple independent cell lines derived from two NSCLC GEMMs one RAF- dependent and one RAS-dependent. This Aim is underway and has verified that KRAS is indeed essential in the KRAS mutant mouse cell lines. Specific Aim 2 To validate our findings in human NSCLC we will test a panel of human NSCLC cell lines with known dependence on RAS for their dependence on the elements hits identified in Aim 1. Study Design In vitro shRNA screen in Aim 1. Individual shRNA validation in human lines in Aim 2.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE