August 11, 2011

VICC investigator lands lung cancer foundation grants

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David Carbone, M.D., Ph.D., and colleagues are working to develop better biomarkers for non-small cell lung cancer tumors. (photo by Anne Rayner)

VICC investigator lands lung cancer foundation grants

David Carbone, M.D., Ph.D., professor of Medicine, Cell and Developmental Biology and Cancer Biology, and colleagues from two University of Texas medical centers have been awarded research grants from the LUNGevity Foundation to develop better predictive biomarkers and treatment protocols for non-small cell lung cancer patients.

Carbone, who leads the Specialized Program of Research Excellence at Vanderbilt-Ingram Cancer Center, will collaborate on the two studies with John Minna, M.D., University of Texas Southwestern, and John Heymach, M.D., Ph.D., from MD Anderson Cancer Center.

The two-year, $100,000 grants were awarded by LUNGevity, a nonprofit foundation with the largest grant awards program of any lung cancer organization in the United States.

Lung cancer is the No. 1 cancer killer in the United States, claiming nearly 160,000 lives each year.

The disease is only curable when found early enough for surgery or combined chemotherapy and radiation, and chemotherapy is toxic for almost all patients.

The investigators want to identify biomarkers to define which non-small cell lung cancer (NSCLC) patients are likely to relapse after surgery, predict who will benefit from adjuvant therapy, and determine what type of adjuvant therapy should be used on each patient.

“This collaboration will take advantage of the unique capabilities of three academic research institutions to determine what is happening at the molecular level in lung cancer,” explained Carbone.

“Vanderbilt has world-class proteomics facilities for analysis of tumor tissues, MD Anderson has unique tissue resources and state-of-the-art reverse-phase protein array technologies and UT Southwestern has investigators who started almost all of the world’s lung cancer cell lines and characterized them for sensitivity to a panel of standard and targeted therapies.”

In the first study, the researchers will study tumor samples resected from early stage lung cancer patients. Despite being found “early,” 30 percent to 40 percent of these patients will suffer relapse and death from these tumors.

Data acquired from these tumor samples will be used to generate tumor-based proteomic and mRNA profiles to define markers that will help identify who will relapse after surgery and also find molecular pathways responsible for this relapse that might be therapeutically targeted to improve the chances for survival of these patients. The researchers will then create a small number of RNA or protein assays to be tested in a larger set of 400 post-surgery patients with and without chemotherapy.

The second study is designed to identify blood-based proteomic markers for predicting response and resistance to vascular endothelial growth factor (VEGF) inhibitor drugs. VEGF is a signaling protein which is important for the growth of blood vessels that feed tumors, a process known as angiogenesis.

Drugs that target tumor blood vessels have improved survival in patients with advanced NSCLC, but only a subset of patients respond to the drugs while other patients experience no benefit or even life-threatening toxicities. Eventually, almost all NSCLC tumors become resistant to these treatments.

“There is a critical unmet need for biomarkers to identify which patients will benefit from a VEGF inhibitor and to understand how tumors become resistant to these agents,” said Carbone.

These investigators believe that by profiling circulating cytokines and angiogenic factors and other peptides in the blood, as well as variations in angiogenesis-related genes, they may be able to develop predictive markers for identifying which patients benefit from VEGF inhibitor drugs.