Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR Mutant and ALK Positive Lung Cancers

Abstract

This project has made very good progress. We have now unveiled an even larger role for defective apoptosis in the emergence of resistance. We have been very successful in our ability to generate cell lines derived from patient biopsies both before treatment and at the time of resistance. We are now using these patient-derived cell lines to assess BIM levels and apoptotic response to next-generation inhibitors. The capacity to develop cell lines from patient biopsies was published in December, 2014 in Science. We have used these models to develop effective combinations to overcome the defect in apoptosis which has led to a CTEP-sponsored clinical trial combining AZD9291 and ABT-263.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2016
Accession Number
AD1030127

Entities

People

  • Jeffrey Engelman
  • Lecia Sequist

Organizations

  • Massachusetts General Hospital

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Apoptosis
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Clinical Trials
  • Genetics
  • Health Services
  • Inhibitors
  • Lung Cancer
  • Mathematical Models
  • Medical Personnel
  • Neoplasms
  • Oncology
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Oncology