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.”