Defining New Treatment Approaches for KRAS-Mutant Lung Cancer

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.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2014
Accession Number
ADA621643

Entities

People

  • Eric Collisson

Organizations

  • University of California, San Francisco

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Cancer
  • Cell Line
  • Cells
  • Colon Cancer
  • Lung Cancer
  • Medical Personnel
  • Neoplasms
  • Patent Applications
  • Professional Development
  • Students
  • Technology Transfer
  • Tumor Cell Line
  • Validation

Fields of Study

  • Biology
  • Medicine

Readers

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  • Oncology