Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents

Area of Science:

• Oncology
• Pharmacology
• Metabolic Diseases

Background:

• Sodium-glucose cotransporter 2 (SGLT2) inhibitors are approved for type 2 diabetes, heart failure, and chronic kidney disease.
• Emerging evidence suggests SGLT2 inhibitors possess anticancer properties independent of glucose-lowering effects.

Purpose of the Study:

• To review the biological rationale and mechanistic insights into the anticancer effects of SGLT2 inhibitors.
• To summarize preclinical and clinical evidence of SGLT2 inhibitors in various cancer types.
• To discuss the potential integration of SGLT2 inhibitors into oncology treatment strategies.

Main Methods:

• Review of preclinical studies on SGLT2 expression and function in cancer cells.
• Analysis of observational cohort studies and randomized controlled trials on cancer risk.
• Evaluation of translational studies on combination therapy with chemotherapy.

Main Results:

• SGLT2 inhibition reduces tumor glucose uptake, disrupts mitochondrial respiration, and induces endoplasmic reticulum stress and autophagy.
• Immunomodulatory effects include PD-L1 degradation and STING-IFN pathway activation.
• Observational studies suggest reduced risk for pancreatic and prostate cancers; clinical trials show neutral overall cancer risk.

Conclusions:

• SGLT2 inhibitors exhibit multifaceted anticancer mechanisms, including metabolic disruption and immunomodulation.
• Clinical evidence suggests a favorable safety profile regarding overall cancer risk.
• SGLT2 inhibitors hold potential as an adjunct therapy in oncology, with early studies indicating feasibility and tolerability with chemotherapy.