Cancer Study Is ‘Paradigm Shift’ in Cause of Tumor Formation

Newswise — PISCATAWAY, NJ – In a new study published in the American Association of Cancer Research’s journal Cancer Research, a pair of investigators at Rutgers and Columbia universities has identified a gene that may provide a new source of potential drug targets for tumors that arise in pulmonary tuberous sclerosis complex (TSC). The discovery may change what is known about tumor formation and help to slow or halt tumor growth, therefore having broader implications in cancer research.

TSC is a rare disorder in which benign tumors grow on vital organs, including the lung, brain, kidneys, eyes and heart. Lymphangiomyomatosis, LAM, which can arise spontaneously or as the pulmonary manifestation of Tuberous Sclerosis Complex is experienced mostly by women of childbearing age in which abnormal muscle tissue invades the lungs and airways.

Building on previous research LAM investigators Kiran Chada, D.Phil. (Oxon.) and Jeanine D’Armiento, MD, PhD, demonstrated in their study that the HMGA2 gene and its signaling pathway (the route of information which begins an action within cells), are required to produce tumors in the lung and kidneys in individuals with TSC.

“Our study of the protein coding gene HMGA2, not only shows that HMGA2 is necessary for the formation of tumors, but its absence completely eliminated tumor formations in animal models of tuberous sclerosis complex,” said Dr. Chada, professor of biochemistry and molecular biology at Rutgers Robert Wood Johnson Medical School.

The researchers’ study also contradicted a long-standing hypothesis that another pathway, mTOR, was essential to tumor growth in TSC and cancer. Unlike the HMGA2 pathway, which was active in 100 percent of all the tumors in TSC, the mTOR pathway was not active in the majority of animal tumors and in less than 50 percent of human tumors in the study.

“We were very surprised, but also excited regarding our investigations, which represent a radically different view on the mechanism of tumor formation in tuberous sclerosis and presents a paradigm shift in our understanding of this syndrome,” said Dr. D’Armiento, associate professor of medicine in anesthesiology, director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics, and director of the Center for LAM and Rare Lung Diseases, College of Physicians and Surgeons at Columbia University.

The discovery of HGMA2’s essential role in tumor development in TSC may have broader implications in other disorders in which tumors appear in multiple sites within the body, including cancer. It also provides a new target for which therapies may be developed to suppress HGMA2 in individuals with TSC and other progressive tumor disorders.

The study was supported by funds from the Columbia University LAM Center and a grant from the Department of Defense (W81XWH-05-1-0184) to Dr. Chada. Dr. D’Armiento is supported by NIH grant RO1-HL086936.

The study may be found at: http://cancerres.aacrjournals.org/content/early/2016/02/02/0008-5472.CAN-15-1287.abstract?sid=c40ce51f-60c9-4d59-ba75-6672195afebc

About Rutgers Robert Wood Johnson Medical SchoolAs one of the nation's leading comprehensive medical schools, Robert Wood Johnson Medical School is dedicated to the pursuit of excellence in education, research, health care delivery, and the promotion of community health. Robert Wood Johnson Medical School and Robert Wood Johnson University Hospital, the medical school's principal affiliate, comprise one of the nation's premier academic medical centers. In addition, Robert Wood Johnson Medical School has 34 other hospital affiliates and ambulatory care sites throughout the region.

Part of Rutgers, The State University of New Jersey, Robert Wood Johnson Medical School encompasses 19 basic science and clinical departments, hosts centers and institutes including The Cardiovascular Institute, the Child Health Institute of New Jersey, and the Women's Health Institute. The medical school maintains educational programs at the undergraduate, graduate and postgraduate levels on its campuses in New Brunswick and Piscataway and provides continuing education courses for healthcare professionals and community education programs. To learn more about Rutgers Robert Wood Johnson Medical School, visit rwjms.rutgers.edu or interact via social media at www.facebook.com/RWJMedicalSchool and www.twitter.com/RWJMS.