Rachel M.A. Linger Ph.D.

This grant is being fully funded by Elliot’s Legacy, through the Uniting Against Lung Cancer Grant Program.

Lay Description

Dr. Linger’s research is focused on the role of a protein called Axl receptor tyrosine kinase in lung cancer. The presence of Axl makes lung cancer cells more invasive and increases the chance that the cancer will spread to other areas in the body. Thus, lung cancer patients with high levels of Axl present in their tumor have a poor prognosis. Dr. Linger believes that the presence of Axl also provides a survival advantage for the lung cancer cells, making them resistant to killing with chemotherapy. Her laboratory has developed inhibitors of the Axl protein and will test whether these inhibitors reduce survival and limit invasiveness of lung cancer cells. Studies will also be conducted to determine whether inhibitors of the Axl protein increase the effectiveness of chemotherapy drugs. If proven correct, these findings could lead to opportunities to provide a more effective treatment for lung cancer.

Scientific Abstract

Dr. Linger’s research is focused on Tyro-3, Axl, and Mer. Together, these three proteins comprise the TAM family of receptor tyrosine kinases (RTKs). The TAM RTKs are aberrantly expressed in several human cancers including leukemia, breast cancer, prostate cancer, glioblastoma, and lung cancer. Studies from other laboratories have demonstrated that expression of Axl correlates with invasive ability of human non-small cell lung cancer (NSCLC) cell lines. Furthermore, in patient samples of NSCLC, Axl overexpression has been statistically associated with metastatic disease. Our preliminary findings demonstrate that TAM RTKs, as well as the ligands which activate them, are co-expressed in many human NSCLC cell lines, suggesting that this family of RTKs may constitute an autocrine loop resulting in constitutive activity of these kinases. Additional preliminary studies indicate that inhibition of Mer or Axl increases the sensitivity of NSCLC cells to killing by chemotherapeutic agents. Using a combination of in vitro biologic assays and in vivo animal models, Dr. Linger hopes to demonstrate that the TAM receptors play key roles in the development and progression of NSCLC. Her laboratory has also developed novel biologic inhibitors of Axl and Mer tyrosine kinases and will test their efficacy in vitro and in animal models of NSCLC. Ultimately, her research using these novel biologic inhibitors may provide a new therapeutic approach for the treatment of NSCLC.