Novel methods to radiosensitize K-ras mutant lung cancer cells

Many patients with non-small cell lung cancer (NSCLC) present with locally advanced disease, which often is treated with radiotherapy plus radiosensitizing chemotherapy. Despite aggressive treatment, rates of local failure are high and overall survival rates are low. The successful use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for tumors with activating mutations in this gene have heralded a new era of targeted NSCLC therapies.

However, 15-30% of tumors harbor activating mutations in K-ras, an oncogene downstream of EGFR. These tumors are resistant to EGFR TKIs, and attempts to directly target mutant K-ras have been largely unsuccessful. Thus, there is great interest in identifying novel strategies to target K-ras mutant NSCLCs. Our laboratory is performing drug screens for novel compounds that selectively radiosensitize K-ras mutant NSCLC cells.

Working closely with Horizon Discovery, Ltd, we are using novel, isogenic WT and K-ras mutant NSCLC cell lines. The identification of novel compounds which selectively kill K-ras mutant cells may lead to the development of new therapies for patients with these tumors, who are desperately in need of targeted therapies.