American Association for Cancer Research

Inhibiting Innate Resistance to Chemotherapy in Lung Cancer Stem Cells


Lung cancer is projected to remain a leading cause of cancer death for the foreseeable future. The most common form of lung cancer is non-small cell lung cancer (NSCLC). Platinum-based chemotherapy drugs are commonly used to treat NSCLC and other cancers, though treatment with these drugs has only limited effect. There is a need to develop new ways to increase the effectiveness of chemotherapy for this disease. Current strategies for developing new drugs for NSCLC rely almost exclusively on testing of candidate agents on established cell lines. A limitation of working with cell lines is that they are usually grown directly on plastic culture dishes in “2D” (growing flat on the plates). Research over the last decade has demonstrated that this method of culturing cells is very different from the conditions that tumor cells experience in a patient. Sweet-Cordero has developed an approach that incorporates the advantages of mouse models and “3D” culture systems to study cancer, and will use this approach as a platform to identify new ways to make chemotherapy more effective at killing lung tumor cells. Using tumor cells isolated from a well-characterized mouse model of lung cancer in which tumors carry one of the most frequent genetic mutations found in human lung cancer (a gene called Kras), he will carry out a screen using a technology called “shRNA,” which allows him to selectively inhibit the action of individual genes. He will test whether loss of specific genes makes cells growing in “3D” more sensitive to chemotherapy. His studies will result in the identification of new targets for drugs that make chemotherapy more effective to treat human lung cancer.


Eric Alejandro Sweet-Cordero, M.D., is assistant professor of pediatrics at Stanford University School of Medicine.

Updated: April 4, 2011