New Diabetes Drugs Sensitise Cancer cells to chemotherapy agents
Scientists from the Dana-Farber Cancer Institute have discovered that experimental diabetes drugs have the potential to increase the vulnerability of cancer cells to traditional chemotherapy treatments. This finding suggests that combining these drugs with chemotherapy could lead to improved outcomes for cancer patients.
In their research, the scientists demonstrated that certain research compounds, similar to thiazolidinediones (TZDs) commonly used as anti-diabetic agents, sensitized lung tumor cells to carboplatin chemotherapy. Animal models treated with a combination of carboplatin and one of the experimental compounds, SR1664, showed smaller tumor sizes compared to those treated with carboplatin alone.
The study also revealed that the combination treatment sensitized triple-negative breast cancer cells in laboratory tests, causing them to self-destruct. However, not all types of cancer cells exhibited increased vulnerability to chemotherapy when combined with the experimental compounds.
The experimental compounds used in the study target a newly discovered cellular process involved in DNA damage repair, which is crucial for the survival of cancer cells. This process involves phosphorylation of a receptor called PPAR-gamma, originally identified as essential for fat cell development by Spiegelman.
PPAR-gamma is also expressed in various cancers, including lung, triple-negative breast, colorectal, and pancreatic cancers. Traditional TZD anti-diabetic drugs, such as rosiglitazone and pioglitazone, target PPAR-gamma. The experimental drugs developed at Scripps, referred to as 'non-canonical agonist ligands' (NAL) of PPAR-gamma, act on this receptor in a different way from conventional TZD drugs.
These NAL compounds retain many properties of TZD drugs but have fewer side effects like weight gain, bone loss, and fluid retention. The phosphorylation of PPAR-gamma identified in this study provides a rational basis for using these NAL compounds to enhance the sensitivity of cancer cells to chemotherapy.
Further research is required to explore the potential of combining these experimental diabetes drugs with chemotherapy in clinical settings and to determine their effectiveness and safety in treating different types of cancers.
These drugs may provide an even safer alternative [than the older TZD anti-diabetes drugs] that you could combine with existing chemotherapies" to enhance the treatment of patients with certain cancers.
