U.S. researchers seem to have untangled the biomarkers behind predicting a response to pemetrexed (Alimta), Eli Lilly's ($LLY) cancer therapeutic, in patients with advanced malignant pleural mesothelioma (MPM), a disease generally caused by exposure to asbestos.
Pemetrexed is used as standard of care and it works by targeting the enzyme thymidylate synthase (TS), which the cancer cells need to replicate. However, not all patients respond to it. While it would seem logical that blocking the enzyme would reduce activity even further and so the drug would be most effective in those people with already low levels of TS, the effects don't seem to be consistent, so it's obviously not quite as simple as that.
To solve the puzzle, the researchers looked at samples of the cancer from 84 people with mesothelioma, and found that low levels only predicted the response to pemetrexed if the levels of folylpoly-γ-glutamate synthetase (FPGS), another enzyme, were high. These were the patients that responded better and survived longer after pemetrexed treatment.
"High levels of FPGS allow pemetrexed to stay longer inside cells, giving the drug longer to work against TS," lead researcher Daniel Christoph said to the Colorado Cancer Blogs.
Knowing this could lead to a test to decide whether patients are treated with pemetrexed or should use a different form of treatment. The next step will be to carry out a study measuring the levels of the two enzymes in mesothelioma patients.