Park Hyun-woo, left, a biochemistry professor at Yonsei College, and Peon Woo-yang, a researcher in Park’s workforce / Courtesy of Yonsei College
A analysis workforce led by Park Hyun-woo, a biochemistry professor at Yonsei College, has launched a pioneering methodology in Oncometabolic Precision Drugs — a breakthrough method that goals to deal with most cancers by focusing on the distinctive approach tumors metabolize vitamins.
The workforce demonstrated {that a} most cancers affected person’s dietary and metabolic standing is a decisive consider figuring out the efficacy of anticancer therapies, providing a brand new therapy framework based mostly on customizing care to take advantage of these metabolic vulnerabilities.
The research discovered that the sensitivity of most cancers cells to medication varies considerably relying on every affected person’s blood metabolite ranges, providing new prospects for customized anticancer therapy tips based mostly on metabolic profiling.
The outcomes had been printed within the newest subject of Most cancers Analysis, the flagship journal of the American Affiliation for Most cancers Analysis.
Park’s workforce constructed a Most cancers Metabolism–based mostly Artificial Lethality Platform by testing 1,813 U.S. FDA-approved non-oncology medication whereas altering concentrations of metabolites typical of the tumor microenvironment — corresponding to glucose, glutamine and fatty acids — and measuring most cancers cell viability.
By way of this platform, the researchers found new molecular mechanisms by which present cardiovascular anti-arrhythmia medication, diabetes drugs and different non-oncology therapies can maximize most cancers cell loss of life relying on metabolic circumstances.
Specifically, the anti-arrhythmic drug propafenone induced cancer-specific cell loss of life solely below low-glucose circumstances, triggering AMPK–mTOR pathway suppression inside most cancers cells. In the meantime, the type-2 diabetes treatment, metformin, inhibited Hippo–YAP signaling, demonstrating anticancer exercise throughout a number of tumor sorts. In contrast, the veterinary anthelmintic fenbendazole confirmed its strongest anticancer results completely below high-glucose circumstances.
These findings present that most cancers cells expertise completely different metabolic stress responses relying on a affected person’s metabolic standing. Clinically making use of such variations might yield a brand new customized therapy technique that reinforces anticancer effectiveness whereas lowering unintended effects.
“This research gives systematic proof that drug responsiveness will be predicted from a affected person’s dietary metabolic map — their blood glucose, fatty acid and amino acid ranges,” Park stated. “It goes past precision drugs that focuses solely on genetic mutations and alerts a shift towards a brand new period of most cancers metabolism–based mostly precision drugs that comes with metabolic profiles.”
