SGLT2 Inhibitors as Potential Anticancer Agents

Area of Science:

• Oncology
• Metabolic Diseases
• Pharmacology

Background:

• Sodium-glucose cotransporter 2 (SGLT2) is overexpressed in cancer, increasing glucose uptake and promoting tumor development.
• SGLT2 inhibitors are antidiabetic drugs with demonstrated anticancer effects across various malignancies.

Purpose of the Study:

• To review SGLT involvement in cancer cell lines.
• To discuss the pharmacology, mechanisms, and applications of SGLT2 inhibitors in reducing tumorigenesis.

Main Methods:

• Literature review assessing SGLT involvement in cancer.
• Analysis of SGLT2 inhibitor pharmacology and mechanisms of action.
• Evaluation of potential therapeutic applications and ongoing clinical trials.

Main Results:

• SGLT2 inhibitors exhibit anticancer effects through multiple mechanisms beyond glucose uptake inhibition.
• Observed anticancer mechanisms include mitochondrial instability, pathway modulation (β-catenin, PI3K-Akt), cell cycle arrest, apoptosis, and altered oxidative phosphorylation.
• SGLT2 inhibitors show varying affinities for SGLT1/SGLT2 and distinct pharmacokinetic profiles.

Conclusions:

• SGLT2 inhibitors present a potential therapeutic strategy against cancer, acting through diverse anticancer mechanisms.
• Combination therapy with SGLT2 inhibitors and standard chemotherapy may offer synergistic benefits.
• Further research is essential to elucidate SGLT expression, subtype activity, and their precise roles in tumor development.