Experimental diabetes drugs could make cancer cells more vulnerable to chemotherapy treatment, potentially improving patient outcomes.
Compounds similar to the diabetes drug class thiazolidinediones (TZDs) have been shown to sensitise lung tumour cells in animal models following chemotherapy with carboplati, a commonly-used chemo drug.
This drug combination also sensitised breast cancer cells in animal models, causing them to self-destruct, and researchers say these combinations should be explored in further detail.
However, not all types of cancer cells appear to be vulnerable to the combination of TZD-similar compounds and carboplati, according to scientists from the Dana-Farber Cancer Institute.
TZDs, also known as glitazones, are an oral type 2 diabetes drug class that help to reduce insulin resistance and improve blood sugar levels. Actos (pioglitazone) is prescribed in the UK for type 2 diabetes, but in 2010 Avandia (rosiglitazone) was banned in the UK after an increased risk of stroke and heart attack was identified.
The compounds used in this study, developed by the Scripps Research Institute Department of Molecular Therapeutics, have similar properties of TZDs but with fewer side effects, such as weight gain and bone loss. The new compounds were investigated for their capability to impact on a cellular process in which cells repair themselves in response to DNA damage.
Specifically, researchers hoped the drugs would impact a change called phosphorylation of PPAR-gamma, a receptor important for fat development. PPAR-gamma is expressed in a variety of cancers, and TZDs are known to combat this change.
Melin Khandekar, MD, PhD, a radiation oncologist at Massachusetts General Hospital, said: “These drugs may provide an even safer alternative [than the older TZD anti-diabetes drugs] that you could combine with existing chemotherapies.”
The scientists, led by Bruce Spiegelma, PhD, a cancer biologist, added “these data strongly suggest that [the experimental anti-diabetes compounds] should be explored for clinical use in combination with traditional chemotherapy for a variety of malignancies”.
The findings have been published in the Proceedings of the National Academy of Sciences journal.

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