Signal Pathway Allows Lung Cancer Cells To Resist Chemotherapy

Trevor G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSFMedicalResearch.com Interview with:
Trever G. Bivona MD PhD
Assistant Professor, Hematology and Oncology
UCSF

Medical Research: What is the background for this study? What are the main findings?

Dr. Bivona: Resistance to targeted cancer therapy remains a problem in the treatment of cancer patients.  These targeted drugs are often effective at shrinking the tumor, but do so incompletely.  This incomplete response results in residual disease that is drug resistant and eventually grows to cause relapse that is lethal in patients.  We investigated the mechanisms underlying this residual disease state in lung cancers treated with the EGFR targeted therapy Tarceva.  We discovered that the tumor cells survival initial EGFR targeted therapy treatment by activating a signaling pathway called NF-kappa B.  This NF-kappa B pathway then promotes tumor cell survival, residual disease, and eventual relapse in the lung cancer models we studied.

Medical Research: What should clinicians and patients take away from your report?

Dr. Bivona:  We can potentially enhance response and overcome resistance to targeted therapy by administering rational targeted drug combinations in the initial treatment setting, to not only block the major cancer driver (such as mutant EGFR in lung cancer) but also the secondary adaptive escape hatch (such as NF-kappa B) to wipe out the tumor completely, eliminate residual disease, and prevent resistance.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Bivona:  We should explore whether NF-kappa B operates more broadly to limit response to targeted therapy more broadly in cancers, and develop clinical agents to selectively block NF-kappa B signaling in appropriately selected cancer patient populations.

Citation:

NF-κB-Activating Complex Engaged in Response to EGFR Oncogene Inhibition Drives Tumor Cell Survival and Residual Disease in Lung Cancer

Blakely, Collin M. et al  Cell Reports April 2015

DOI: http://dx.doi.org/10.1016/j.celrep.2015.03.012

 

 

MedicalResearch.com Interview with: Trevor G. Bivona MD PhD (2015). Signal Pathway Allows Lung Cancer Tumor Cells To Resist Chemotherapy