Blog: Decoding the Research

Meet our grantees: Dr. Steven H. Lin, University of Texas MD Anderson Cancer Center

Published: April 23rd, 2013

Kras mutation targeting to enhance radiation response in non-small cell lung cancer

Though much progress has been made, lung cancer is still the leading cause of cancer death in the US. Radiation therapy combined with chemotherapy remains a powerful method to treat lung cancer, but is not always completely effective.  Dr. Lin is investigating radiation therapy combined with targeted therapies, with the goal of reducing toxicity and improving efficacy.

Approximately 30% of patients with non-small lung cancers have tumors driven by mutations to the KRAS gene.  Most of the treatment approaches in advanced, metastatic KRas+ lung cancers have focused on combining targeted agents with chemotherapy. However, there have been little to no clinical studies that combine targeted therapies with chemoradiation. We need strategies that can enhance both radiation effects to kill the bulky tumor locally and also control undetectable metastatic disease.

Dr. Lin will be using a targeted MEK inhibitor (trametinib), that acts downstream of KRas signaling to sensitize cancer cells to radiation therapy.  A significant part of this research is using biomarkers that can help select the right patients for optimal treatment. An in-depth understanding of how tumors with different genetic mutations respond differently to targeted therapies could lead to better personalized treatment approaches.

For his grant research, Dr. Lin will essentially conduct a “co-clinical”  trial along with an ongoing phase I study that is testing combining tramatinib with standard chemoradiation. He will be examining how cancer cells with different genetic mutations respond differently to treatment with tramatinib and radiation in both cell lines and pre-clinical models.

Learning from experiments using good preclinical models, this work will provide crucial data for future clinical trials of chemoradiation plus trametinib in patients with Stage III Kras-mutated non-small cell lung cancers.  

Dr. Lin is an Assistant Professor in the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston. Dr. Lin’s grant is sponsored by The Sidney Kimmel Foundation.

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