03:41am Thursday 21 September 2017

Scientists Identify Strategy to Prevent Renal Failure, Also Hit on Opportunities to Improve Cancer Treatment

BUFFALO, N.Y. — Acute kidney injury (AKI), also known as acute renal failure, is one of the main contributors to death and disability worldwide, yet no preventive treatment for the condition has been established. In a new study published in the journal Cell Death and Differentiation, a team of researchers led by scientists from Roswell Park Cancer Institute (RPCI) reports that they have identified 10 genes whose inhibition appears to protect kidney cells. The findings point the way to strategies for preventing AKI, perhaps through treatment with existing, well-tolerated drugs, and may also help to evade drug resistance in cancer therapy.

AKI is often prompted by ischemia, or loss of blood flow, which restricts the supply of oxygen and nutrients to the affected tissues. “It is a global clinical problem with increasing incidence, dire consequences, unsatisfactory therapeutic options, and an enormous financial burden to societies worldwide,” the authors write. The mortality of those who experience AKI, they note, “may approach or even exceed 50 percent, and those that survive face prolonged hospitalization and significant increases in morbidity.”

The research team, led by Eugene Kandel, PhD, Assistant Member and Assistant Professor of Oncology in the Department of Cell Stress Biology at Roswell Park, used high-throughput functional-genomics technology to uncover 10 genes, interference with which protects kidney epithelial cells in ischemia-like conditions. Further experiments have shown that chemical inhibition of the product of one of the genes — TACR1 — reduces the extent of ischemic AKI in laboratory models. The team also found that some of these same genes are involved in how cells respond to not only ischemia but other damaging stresses as well, including those triggered by anti-cancer therapy.

“We are looking forward to clinical translation of our work,” says Dr. Kandel. “A lot of preclinical and clinical testing is yet to be done, but it is encouraging that well-characterized drugs that target the product of TACR1 gene already exist. Our findings also give some clues as to how tumor cells could tolerate ischemia-like conditions and why some cancers don’t respond well to therapy. In the long term, this knowledge may help us to match cancer therapy to the pre-existing mutations in a given tumor in order to overcome drug resistance and prevent harmful side effects.”

The study was supported in part by the Roswell Park Alliance Foundation. Five of the paper’s seven authors are employees of F. Hoffmann-La Roche AG, which also provided funds in support of this work.

The paper, entitled “An RNA interference screen identifies new avenues for nephroprotection,” is available at Nature.com.

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The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.
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