Sitagliptin and Cancer Immunotherapy

Sitagliptin is a drug that is commonly used to treat type 2 diabetes. It works by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), which can lead to increased levels of the hormone glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion and can improve glucose control.

While sitagliptin is not typically used as a cancer treatment, there is some research suggesting that it may have potential as an immunotherapy agent for cancer. In preclinical studies, sitagliptin has been shown to enhance the anti-tumor immune response and increase the infiltration of immune cells into the tumor microenvironment.

PD-1 (programmed cell death protein 1) is another protein that is expressed on the surface of T cells and acts as a negative regulator of the immune response. Antibodies that block PD-1 or its ligand, PD-L1, have been shown to be effective in the treatment of several types of cancer.

There is some research suggesting that sitagliptin may enhance the activity of both CTLA-4 and PD-1 blockade in cancer immunotherapy. For example, a study published in the journal Cancer Immunology Research in 2018 showed that treatment with sitagliptin enhanced the anti-tumor immune response and improved the efficacy of PD-1 blockade in mouse models of lung cancer.

The researchers suggested that sitagliptin may enhance the activity of CTLA-4 and PD-1 blockade by modulating the immune system and increasing the infiltration of immune cells into the tumor microenvironment. In addition, sitagliptin has been shown to increase the expression of PD-L1 on cancer cells, which may sensitize them to PD-1 blockade.

While these findings are promising, more research is needed to fully understand the potential benefits of sitagliptin in combination with CTLA-4 and PD-1 blockade, and to determine the most effective doses and formulations for use in cancer patients. Clinical trials evaluating the use of sitagliptin in combination with immune checkpoint inhibitors are currently underway.

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Williams Cancer Institute

Tuesday, March 28, 2023