BATTLE Links Potential Biomarkers to Lung Cancer Drugs
Results of the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) indicate a paradigm shift for clinical trials, say MD Anderson researchers, who shared their findings recently in Washington, D.C., during the 101st annual meeting of the American Association for Cancer Research.
BATTLE is the first lung cancer clinical trial to guide targeted therapies to patients based on molecular signatures in tumor biopsies. The study, conducted at MD Anderson and funded through the U.S. Army’s medical research program, used an innovative statistical model to match four drugs to specific molecular biomarkers in the tumors of 255 stage IV non-small cell lung cancer patients who had received between one and nine previous treatments. The first 97 patients were equally randomized to BATTLE's four arms. As the study progressed, the model used information from patients’ biopsies and outcomes to guide assignment of drugs to new patients, who became more likely to receive a drug that had worked for earlier patients with the same tumor biomarkers.
BATTLE not only has demonstrated the feasibility of a biopsy-based, hypothesis-driven biomarker trial, the MD Anderson researchers say, but also has made a significant step toward personalized care and more effective, efficient clinical trials.
“BATTLE evaluated tumor biomarkers in hopes that we can treat lung cancer, which kills more people than any other type of cancer, like we treat breast or colon cancer, using validated biomarkers to guide treatment and improve survival,” says Edward Kim, M.D., associate professor in MD Anderson’s Department of Thoracic/Head and Neck Medical Oncology and principal investigator on the BATTLE clinical trials. Roy Herbst, M.D., Ph.D., professor in the Department of Thoracic/Head and Neck Medical Oncology, is co-principal investigator on the BATTLE clinical trials.
“Two lung cancer tumors might appear identical under a microscope, but they behave differently,” says Waun Ki Hong, M.D., head of MD Anderson’s Division of Cancer Medicine and principal investigator on the BATTLE grant from the U.S. Department of Defense. “The name of the game now is to treat based on the molecular defects in the tumor.”
Kim says future BATTLE trials will test combinations of therapies as well as single agents and will concentrate on the entire range of staging for lung cancer patients, including frontline therapy. Ultimately, the researchers plan to try the BATTLE approach in personalizing prevention clinical trials.
BATTLE was established in 2000 in honor of R. Duffy Wall, a lung cancer patient at MD Anderson who lost his life to the disease. Private philanthropy has played a major role in supplementing federal funds for the program.
Gene Study Provides Major Clue in Cancer Metastasis
An international team led by scientists at MD Anderson has identified the molecular machinery that switches on a gene known to cause breast cancer to spread and invade other organs.
The discovery provides a target-rich environment for development of drugs to thwart expression of the RhoA gene, says Hui-Kuan Lin, Ph.D., an assistant professor in MD Anderson’s Department of Molecular and Cellular Oncology. RhoA overexpression has been implicated in cancer metastasis.
“There are four components to this complex, which starts RhoA expression by transcribing the gene, and we found that all of them are important to metastasis,” says Lin, senior author of a paper reporting these findings online in Nature Cell Biology. “Knock down any one of the four, and you can stop breast cancer metastasis by preventing RhoA expression.”
Funding for this research comes from MD Anderson’s Research Trust Scholar funds, the National Cancer Institute’s Prostate Cancer Specialized Program in Research Excellence at MD Anderson and a Department of Defense New Investigator Award to Lin.