SGLT-2 Inhibitors in Cancer Treatment—Mechanisms of Action and Emerging New Perspectives

SIMPLE SUMMARY: Despite significant advances in the treatment of cancer, it remains a major cause of death worldwide and new treatment options are constantly being sought. An interesting new group of antidiabetic drugs, called sodium-glucose cotransporter 2 inhibitors have beneficial effects in patients with heart failure and slow the progression of renal failure. They have recently been shown to additionally exhibit anticancer effects in certain types of cancer. The mechanism of their anticancer action, however, is not yet fully understood. Research into understanding these mechanisms is ongoing and it is hoped that, in the future, this knowledge may be used to develop new cancer treatments using these drugs. The possibility of using this group of drugs in anticancer treatment seems very attractive, especially as they are already used in the treatment of diabetes and heart failure. This article presents the mechanisms of their anti-cancer action which are so far known. ABSTRACT: A new group of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors), have recently been shown to have anticancer effects and their expression has been confirmed in many cancer cell lines. Given the metabolic reprogramming of these cells in a glucose-based model, the ability of SGLT-2 inhibitors to block the glucose uptake by cancer cells appears to be an attractive therapeutic approach. In addition to tumour cells, SGLT-2s are only found in the proximal tubules in the kidneys. Furthermore, as numerous clinical trials have shown, the use of SGLT-2 inhibitors is well-tolerated and safe in patients with diabetes and/or heart failure. In vitro cell culture studies and preclinical in vivo studies have confirmed that SGLT-2 inhibitors exhibit antiproliferative effects on certain types of cancer. However, the mechanisms of this action remain unclear. Even in those tumour cell types in which SGLT-2 is present, there is sometimes an SGLT-2-independent mechanism of anticancer action of this group of drugs. This article presents the current state of knowledge of the potential mechanisms of the anticancer action of SGLT-2 inhibitors and their possible future application in clinical oncology.