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

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...

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Published in:European journal of pharmacology Vol. 978; p. 176803
Main Authors: Naeimzadeh, Yasaman, Tajbakhsh, Amir, Nemati, Mahnaz, Fallahi, Jafar
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 05.09.2024
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Breast neoplasms
Breast Neoplasms - drug therapy
Clinical Trials as Topic
Diabetes mellitus
Female
Gene mutations
Humans
Precision medicine
SGLT2 inhibitor
Sodium-Glucose Transporter 2 Inhibitors - pharmacology
Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
Breast neoplasms
Gene mutations
Precision medicine
Antineoplastic agents
SGLT2 inhibitor
Diabetes mellitus
ISSN:0014-2999, 1879-0712, 1879-0712
Online Access:Get full text
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Summary: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. [Display omitted] •SGLT2 inhibitors have shown anti-cancer properties in breast cancer treatment.•Specific SGLT2 inhibitors have demonstrated the ability to inhibit breast cancer cell proliferation.•SGLT2 inhibitors have been found to induce apoptosis in breast cancer cells, potentially contributing to tumor reduction.•These inhibitors have shown a potential to enhance the effectiveness of chemotherapy or targeted therapy in breast cancer treatment.•SGLT2 inhibitors can overcome chemo-resistance and improve outcomes for challenging breast cancer.
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ISSN:0014-2999
1879-0712
1879-0712
DOI:10.1016/j.ejphar.2024.176803