Researchers have found a new test that can detect changes in the levels of metabolites in the blood and help identify whether a cancer drug is working as designed or not. According to researchers, cancer drugs affect the amount of metabolites — the building blocks of fats and proteins — present in the blood of patients with the deadly disease. “Our study is an important step in the development of new precision cancer therapies and is the first to show that blood metabolites have real potential to monitor the effects of novel agents,” said Florence Raynaud from The Institute of Cancer Research in Britain.
The study investigated the metabolic markers that could accurately assess how cancers were responding to the targeted drug pictilisib. Pictilisib is designed to specifically target a molecular pathway in cancer cells — called PI3 kinase — which has a key role to play in cell metabolism and is defective in a range of cancer types. As cancers with PI3K defects grow, they cause a decrease in the levels of metabolites in the bloodstream. For the study — published in the journal Molecular Cancer Therapeutics — the team measured the levels of 180 blood markers in 41 patients with advanced cancers in a phase I clinical trial conducted both in pre-clinical mouse models and also in humans. In the mice study, the findings showed an increase in the presence of 26 different metabolites in the bloodstream of mice that were given pictilisib, which were low prior to the therapy.
This indicated that the drug was hitting its target as well as reversing the effects of the cancer on mouse metabolites. In the trial conducted on humans, 22 out of the 26 metabolites increased in response to the pictilisib therapy. A single dose of pictilisib increased the blood levels of the metabolites, however, when the treatment stopped a resultant decrease was noted, suggesting that the effect was directly related to the introduction of pictilisib. “Our method could eventually be used to monitor patients routinely during the course of treatment as a quick and easy way of assessing whether a drug is still working, or whether treatment needs to be adapted,” added one of the researchers Paul Workman, Professor at The Institute of Cancer Research. The new way of monitoring cancer therapy could speed up the development of new-targeted drugs which exploit specific genetic weaknesses in cancer cells and help in modifying treatment for patients, the researchers concluded.