Researchers, for the first time, have found that the level of blood metabolites, the building blocks of fats and proteins, are "testable indicators" of whether or not a cancer treatment is working accurately, an advance that could help in tailoring treatment for patients.
Researchers, for the first time, have found that the level of blood metabolites, the building blocks of fats and proteins, are “testable indicators” of whether or not a cancer treatment is working accurately, an advance that could help in tailoring treatment for patients.
This 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 tailoring treatment for patients, researchers said.
Scientists from the Institute of Cancer Research (ICR) in the UK measured the levels of 180 blood markers in 41 patients with advanced cancers.
They found that investigating the mix of metabolic markers 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 key a role in cell metabolism and is defective in a range of cancer types, researchers said.
“The new study is the first to show that blood metabolites are testable indicators of whether or not a new cancer treatment is hitting the correct target, both in preclinical mouse models and also in a trial of patients,” they said.
Using a sensitive technique called mass spectrometry, scientists initially analysed the metabolite levels in the blood of mice with cancers that had defects in the PI3K pathway.
They found that the blood levels of 26 different metabolites, which were low prior to therapy, had risen considerably following treatment with pictilisib.
Their findings indicated that the drug was hitting its target, and reversing the effects of the cancer on mouse metabolites, researchers said.
Similarly, in humans, scientists found that almost all of the metabolites – 22 out of the initial 26 – once again rose in response to pictilisib treatment, as seen in the mice.
Blood levels of the metabolites began to increase after a single dose of pictilisib, and were seen to drop again when treatment was stopped, suggesting that the effect was directly related to the drug treatment, researchers said.
“We have shown that assessing a patient’s metabolites can be a quick and simple way of assessing whether a cancer drug is specifically hitting its intended target in the body,” said Florence Raynaud from ICR.
“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 Raynaud.
The findings were published in the journal Molecular Cancer Therapeutics.