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Autophagy Defect Explored in Hereditary Breast Cancer

Rutgers Cancer Institute of New Jersey investigators awarded $2.4M for research
June 22, 2015

Bing Xia, PhD and Eileen White, PhDNew Brunswick, N.J. – Rutgers Cancer Institute of New Jersey researchers Bing Xia, PhD, and Eileen P. White, PhD, have been awarded a $2.4 million R01 grant (R01CA188096) from the National Cancer Institute (NCI) to explore the relationship between the cellular-survival mechanism of autophagy and tumor suppression function in hereditary breast cancers.

Mutations in the BRCA1 and BRCA2 genes account for nearly a quarter of hereditary breast cancers and about five percent of all breast cancers, according to the NCI. These genes produce tumor suppressor proteins that help repair damaged DNA – the material that makes up one’s genes.  When BRCA1 and BRCA2 genes are mutated and their respective tumor suppressor proteins affected, DNA repair may not take place properly. As a result, normal cells can develop into cancer cells.  Another gene that has a critical function in the same tumor suppression pathway is PALB2, first discovered by Dr. Xia in 2006. The PALB2 protein physically links together BRCA1 and BRCA2 proteins to suppress breast cancer development.

Just as DNA damage can cause cancer to form, too much DNA damage can kill pre-cancerous cells and prevent cancer development.  Breast cells are placed in this situation when BRCA1, BRCA2 or PALB2 proteins are lost.  In this case, the cells activate p53, another tumor suppressor that halts the growth of damaged cells.  In order for these cells to overcome the tumor suppressor ability of p53, they appear to hijack a cell survival mechanism known as autophagy that disposes of toxic wastes, recycles cell nutrients and mitigates stresses.  Taking advantage of this process, rogue cells can multiply and evolve into cancer cells.  The grant awarded to Drs. Xia and White will enable them to further explore and model autophagy defect in PALB2 and in BRCA1- and BRCA2-associated hereditary breast cancers and test the potential of blocking autophagy for the prevention and treatment of these cancers.  

“As a result of seminal discoveries on the DNA repair function of proteins, the repair defect of the BRCA-mutant tumor cells is now being targeted using platinum drugs and poly (ADP-ribose) polymerase (PARP) inhibitors. However, the tumor cells tend to develop resistance to both types of drugs. Therefore, for both prevention and better treatment of BRCA- and PALB2-associated breast cancers, it is imperative to find new avenues to selectively kill the mutant cells, preferably ones that target pathways other than DNA repair,” says Xia, who is also an associate professor of radiation oncology and pharmacology at Rutgers Robert Wood Johnson Medical School.

“Blocking the autophagy survival mechanism in these BRCA- and PALB2-associated breast cancers may be a new option,” notes White, an internationally-recognized leader in autophagy research, who is also associate director for basic science at the Cancer Institute of New Jersey and a distinguished professor of molecular biology and biochemistry at Rutgers School of Arts and Sciences.

The project period runs through May 2020.

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 848-932-3637 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 and Carol G. Simon Cancer Center at Overlook Medical Center. Affiliate Hospitals: JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), and Robert Wood Johnson University Hospital Somerset.

 

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