SGLT-2 inhibitors beyond diabetes: a new frontier in cancer treatment

Abstract

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, a new class of antidiabetic medications including canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, recently came to light as possible anti-cancer therapeutics. The confirmed presence of SGLT-2 in many cancer cell lines further substantiates their potential as therapeutic targets. Because many cancer cells change their metabolism to become more glucose-dependent, blocking glucose absorption with SGLT-2 inhibitors is an intriguing anti-cancer therapy. In addition to their physiological function in renal proximal tubules, SGLT-2 has been identified in specific tumor cells. Clinical trials have shown that SGLT-2 inhibitors are safe and well-tolerated in individuals with diabetes and heart failure. Significantly, these medicines demonstrate antiproliferative effects across multiple cancer types, as substantiated by both in vitro and in vivo models, frequently via mechanisms that are independent of SGLT-2 itself. They seem to regulate a diverse array of intracellular and extracellular signaling pathways, encompassing those associated with microRNAs, AMPK, ERK, DNA and RNA metabolism, ATP homeostasis, and mitochondrial function. These data collectively underscore the potential of SGLT-2 inhibitors in clinical oncology and elucidate the processes driving their anti-cancer efficacy.