Researchers at UCLA have discovered that inhibiting SGLT2 in pancreatic and prostate adenocarcinomas can reduce cancer cell survival.
One reason for the unsustainable growth of tumors is their independence from regulatory pathways that ensure normalcy of cellular metabolism. However, activation of oncogenes and loss of tumor suppressors in cancer promote metabolic reprogramming, resulting in enhanced nutrient uptake and cancer progression. Intervention with these metabolic pathways could potentially provide a therapeutic advantage to prevent resistance to chemotherapy or radiotherapy.
Now, researchers at the University of California in Los Angeles have discovered that pancreatic and prostate adenocarcinomas express the glucose transporter SGLT2 (sodium-dependent glucose transporter), which actively imports glucose into cancer cells. Inhibiting SGLT2, the authors claim in their paper published in the Proceedings of the National Academy of Sciences, could be useful in cancer treatment.
“This is exciting because it provides strong evidence that SGLT2 inhibitors, such as those currently approved by the FDA to treat diseases like diabetes, could potentially block glucose uptake and reduce tumor growth and survival in pancreatic and prostate cancers,” said Dr Ernest Wright, professor of physiology and lead author of the study, in an interview.
The researchers first used surgical tumor specimens to conduct transporter assays—this confirmed the expression of SGLT2 in human pancreatic and prostate cancers. Then, using a mouse xenograft model of pancreatic cancer, the authors examined tumor growth and survival in the presence and absence of SGLT2 inhibitors (canagliflozin and dapagliflozin) currently approved for the treatment of type 2 diabetes mellitus, along with gemcitabine which is used in the treatment of pancreatic cancer. The results showed that treatment with the SGLT2 inhibitors either reduced the rate of tumor growth in mice or increased tumor necrosis, potentiating the effect of gemcitabine.
The authors plan to follow-up their study with a clinical trial to test SGLT2 inhibitors in pancreatic and prostate cancer patients.
Pancreatic cancer is the fourth-leading cause of cancer-related death in the United States, with a mortality that nearly matches disease incidence and a dismal 5-year survival rate of 7%. Prostate cancer follows lung cancer as the second leading cause of cancer-related death among men in the United States.