Newswise — New Brunswick, N.J., June 24, 2014 –According to the National Cancer Institute, more than a third of all human cancers, including a high percentage of pancreas, lung and colon cancers are driven by mutations in a family of genes known as Ras. Ras has long been considered to be a target that does not respond to cancer treating drugs, but recent research suggests new possibilities. Investigators at Rutgers Cancer Institute of New Jersey have demonstrated that targeting a metabolic dependency downstream of Ras could provide therapeutic benefit to patients with Ras-driven lung cancers.
Activation of oncogenic Ras promotes tumor growth but also activates the cellular self-cannibalization process of autophagy that recycles intracellular components to help sustain that growth. In research published in the current online edition of Cancer Discovery (doi: 10.1158/2159-8290.CD-14-0363), senior author Eileen White, associate director for basic science at the Cancer Institute of New Jersey, and colleagues tested the consequence of removing the autophagy gene known as ATG7 from laboratory models with non-small-cell lung cancer. Their goal was to establish if systemic genetic inactivation of autophagy would have selective anti-tumor activity against Ras-driven lung cancers while sparing most normal tissues. If so, then this would provide evidence that therapeutically targeting autophagy would be a new approach to treat these cancers.
Their research showed that systemic loss of ATG7 caused loss of fat tissue and sensitivity to fasting, but few other damaging consequences to normal tissue in the short-term. In contrast to most normal tissues, switching off autophagy by deleting ATG7 was dramatically destructive to established non-small-cell lung cancers. This demonstrated that non-small-cell lung cancer selectively requires autophagy for tumor development and that therapeutically targeting autophagy may be an alternative to targeting Ras.
One of the challenges in administering cancer therapy is that the treatment designed to destroy the disease can also have a negative effect on healthy, normal tissue. “The anti-tumor activity seen in our study occurred prior to the destruction of normal tissue. This suggests that the action of selectively and deliberately blocking the autophagy process may have therapeutic benefit for non-small-cell lung cancer and other Ras-driven cancers,” notes Dr. White, who is also a distinguished professor of molecular biology and biochemistry at Rutgers School of Arts and Sciences.
White and colleagues will work with other collaborators at the Cancer Institute to develop early-phase patient clinical trials based on the findings from this study in the near future. Other authors on the study include: Gizem Karsli-Uzunbas, Jessie Yanxiang Guo, Sandy Price, all Cancer Institute; Xin Teng, Princeton University; Saurabh V. Laddha, Sinan Khor, both Cancer Institute; Nada Y. Kalaany, Harvard Medical School; Tyler Jacks, MIT; Chang S. Chan, Cancer Institute and Joshua D. Rabinowitz, Princeton University and Cancer Institute.
The work was supported by funding from the Cancer Institute (P30 CA072720), National Institutes of Health (R37 CA53370 and R01 CA130893, White; RC1 CA147961 and R01 CA163591, Rabinowitz, White), and the Val Skinner Foundation.
About Rutgers Cancer Institute of New Jersey
Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, the Cancer Institute of New Jersey is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention. Physician-scientists at the Cancer Institute engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 732-235-8614 or visit www.cinj.org/giving. Follow us on Facebook at www.facebook.com/TheCINJ.
The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. System Partner: Meridian Health (Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, Southern Ocean Medical Center, and Bayshore Community Hospital). Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Medical Center, Carol G. Simon Cancer Center at Overlook Medical Center, and Cooper University Hospital. Affiliate Hospitals: JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), Robert Wood Johnson University Hospital Somerset, Shore Medical Center, The University Hospital and University Medical Center of Princeton at Plainsboro.