An acid test for metformin^†

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Highly glycolytic cancer cells rely on lactic acid export for homeostasis.
• Monocarboxylate transporters (MCTs), specifically MCT1 and MCT4, are key in this process.
• Syrosingopine inhibits MCT1 and MCT4, presenting a potential therapeutic target.

Purpose of the Study:

• To investigate the combined therapeutic effect of syrosingopine and metformin on multiple myeloma (MM).
• To evaluate the synergistic potential of targeting lactate transport in cancer cells.

Main Methods:

• Utilized cultured multiple myeloma cell lines.
• Tested the drug combination on primary MM blasts from patients.
• Employed a mouse model of multiple myeloma.

Main Results:

• Syrosingopine and metformin demonstrated a synergistic effect in killing MM cells.
• The combination therapy was effective against both cultured cell lines and patient-derived primary cells.
• The synergistic effect was also observed in a preclinical mouse model of MM.

Conclusions:

• The combination of syrosingopine and metformin exhibits synthetic lethality in multiple myeloma.
• These drugs, with established safety profiles, offer a potential clinical strategy for anticancer therapy.
• Targeting lactate transport via MCT inhibition presents a viable therapeutic approach for multiple myeloma.