Study: Cancer drug may cause metabolic imbalance, shorter survival

By Matthew Worley

Sept. 26 (UPI) -- A new study suggests that the cancer drug nivolumab, a checkpoint blocker drug, may trigger a metabolic imbalance in patients treated with the drug.

This imbalance, researchers say in the study, published in the journal Nature Communications, may trigger resistance to immunotherapy agents, leading to shorter overall survival times.


For the study, scientists at the Dana-Farber Cancer Institute, collaborating with the Broad Institute of MIT and Harvard, analyzed blood samples from three independent immunotherapy trials.

The analysis was designed to measure changes in chemicals involved in the body's metabolic reactions. Researchers found that 78 percent of melanoma patients experienced an increase in the tryptophan to kynurenine conversion, and 26.5 percent showing increases of more than 50 percent after four weeks of treatment. In kidney cancer patients, nivolumab was also associated with increases in kynurenine.

The analysis showed that nivolumab patients with higher levels of tryptophan to kynurenine conversion had poorer survival rates.

The exact process by which nivolumab works isn't known. However, an enzyme known as IDO, implicated in many forms of cancer, plays a major role in synthesizing kynurenine from tryptophan.

The study, researchers said, suggests that combining checkpoint blockers with IDO inhibitors might "benefit a selected group of patients with checkpoint-inhibition-triggered kynurenine pathway activation."


"The main message is that metabolic adaptations in cancer immunotherapy may be relevant after immune checkpoint blockade," said Toni K. Choueiri, co-senior author of the paper.

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