Researchers report a link between tumor metabolism and how well cancer drugs work. Finding drugs that kill cancer cells but spare normal cells is a key aim of precision medicine. The new study focuses on PRMT5, a gene-regulating protein and long-standing drug target.
In normal cells PRMT5 binds the metabolite SAM. In tumor cells with mutation or deletion of MTAP, PRMT5 instead binds MTA. This change occurs in roughly 10 to 15 percent of cancers and creates a vulnerability that drugs can exploit to target MTAP-deficient tumors.
The teams used a biosensor approach based on Promega's NanoBRET technology to measure drug binding to the MTA-bound form of PRMT5. The University of Oxford designed a probe, CBH-002, that reports target engagement with a PRMT5‑NanoLuc biosensor in live cells and showed sensitivity to metabolite levels.
Authors say the results point to a new class of tumor-specific drugs and the work involved collaboration among several universities and Promega, with support from the NIH.
Difficult words
- metabolism — chemical processes in a living cell
- metabolite — small molecule produced by metabolism
- vulnerability — a weakness that drugs can attack
- biosensor — device that measures biological signals in cells
- probe — a tool used to find or measure
- precision medicine — medical treatment tailored to a patient
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could drugs that target MTAP-deficient tumors help patients compared with standard treatments?
- Why do you think measuring drug binding in live cells is useful for developing new cancer drugs?
- The article mentions collaboration among universities and a company. What are advantages of such collaborations in medical research?
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