Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies.

Autor: Naeimzadeh Y; Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 7133654361, Iran., Tajbakhsh A; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: Tajbakhsh.amir921@gmail.com., Nemati M; Amir Oncology Hospital, Shiraz University of Medical Sciences, Shiraz, Iran., Fallahi J; Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 7133654361, Iran. Electronic address: jafarf80@gmail.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Sep 05; Vol. 978, pp. 176803. Date of Electronic Publication: 2024 Jun 29.
DOI: 10.1016/j.ejphar.2024.176803
Abstrakt: The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer (BC) has prompted the exploration of novel therapeutic strategies targeting shared metabolic pathways. This review focuses on the emerging evidence surrounding the potential anti-cancer effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in the context of BC. Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of BC cells, induce apoptosis, and modulate key cellular signaling pathways. These mechanisms include the activation of AMP-activated protein kinase (AMPK), suppression of mammalian target of rapamycin (mTOR) signaling, and regulation of lipid metabolism and inflammatory mediators. The combination of SGLT2 inhibitors with conventional treatments, including chemotherapy and radiotherapy, as well as targeted therapies like phosphoinositide 3-kinases (PI3K) inhibitors, has shown promising results in enhancing the anti-cancer efficacy and potentially reducing treatment-related toxicities. The identification of specific biomarkers or genetic signatures that predict responsiveness to SGLT2 inhibitor therapy could enable more personalized treatment selection and optimization, particularly for challenging BC subtypes [e, g., triple negative BC (TNBC)]. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive BC care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of BC, including the aggressive and chemo-resistant TNBC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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