Researchers Discover New Combination of Two Previously Approved FDA Drugs to Treat Lung Cancer

Newswise — Cleveland -- A team of researchers led by Dr. Goutham Narla at Case Western Reserve University School of Medicine in collaboration with scientists at Mount Sinai School of Medicine in New York, have discovered a previously unrecognized signaling network disrupted in lung cancer that can be turned back on by a novel combination of two previously approved FDA drugs. The drug combination targets a pathway to treat advanced/late stage lung cancer. The work highlights how understanding the basic mechanisms regulating cancer development and progression can lead to new uses for existing FDA approved drugs in the treatment of cancer.

“Because of the financial constraints and length of time it takes to bring new drugs through clinical trials, scientists are moving toward using existing drugs in new ways so that the process of translating the discoveries of today into the treatments of tomorrow can be accelerated,” said Goutham Narla, MD, PhD, assistant professor, Department of Medicine, Institute of Transformative Molecular Medicine, Case Western Reserve University School of Medicine. Dr. Narla is also a medical geneticist at University Hospitals Case Medical Center.

“This ‘movement’ in science toward using existing FDA approved drugs for new purposes in the treatment of cancer has expanded our understanding of the pathways that cause the disease and significantly accelerates our ability to treat a greater number of patients. In many instances, every month makes a difference for a patient when dealing with terminal cancer,” said Dr. Narla.

Dr. Narla’s laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Dr. Narla and his team have identified new signaling pathways regulated by this gene family thus providing new insight into cancer diagnosis and treatment. The team’s research found that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. By using a combination of two existing FDA drugs - Erlotinib, a targeted cancer drug, and Trifluoperazine, a medication used to treat schizophrenia - the team developed an understanding of the properties that turn these critical genes back on, initiating tumor cells to die.

Since first discovering the KLF6 gene 13 years ago as a medical student at the Mount Sinai School of Medicine in the laboratory of Dr. Scott Friedman, Dr. Narla has been involved in the identification and characterization of the KLF6 gene and its role in cancer development and the progression of cancer.

This study appears online in the Journal of Clinical Investigation.

Additional support for Dr. Narla’s research comes from the Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Case Western Reserve University Institute for Transformative Molecular Medicine, and the Mount Sinai School of Medicine. Dr. Narla is also

supported by an early physician scientist career award from the Howard Hughes Medical Institute (HHMI).

Recently, Dr. Narla has also been named the first Harrington Distinguished Scholar. This inaugural award provides physician-scientists who have potential breakthroughs with the ability to tap into grant funding, as well as a peer network of innovators and mentors within the University Hospitals Harrington Discovery Institute’s infrastructure to support their discovery efforts

Dr. Narla is the principal investigator leading a multidisciplinary team with investigators at both the Mount Sinai School of Medicine and the Case Western Reserve University School of Medicine that includes Jaya Sangodkar, Neil S. Dhawan, Heather Melville, Varan J. Singh, Eric Yuan, Huma Rana, Sudeh Izadmehr, Caroline Farrington, Sahar Mahzar, Suzanna Katz, Tara Albano, Pearlann Arnovitz, Rachael Okrent, Michael Ohlmeyer, David Burstein, David Zhang, Katerina Politi and Analisa DiFeo.

About Case Western Reserve University School of Medicine Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the school of medicine. Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report “Guide to Graduate Education.”

The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.

About Case Comprehensive Cancer CenterCase Comprehensive Cancer Center is an NCI-designated Comprehensive Cancer Center located at Case Western Reserve University. The center, now in its 22nd year of funding, integrates the cancer research activities of the largest biomedical research and health care institutions in Ohio – Case Western Reserve, University Hospitals (UH) Case Medical Center, Cleveland Clinic and MetroHealth Medical Center. NCI-designated cancer centers are characterized by scientific excellence and the capability to integrate a diversity of research approaches to focus on the problem of cancer. It is led by Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the National Center for Regenerative Medicine, Case Western Reserve, and director of the Seidman Cancer Center at UH Case Medical Center.