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This investigational combination therapy pairs the biguanide antidiabetic agent metformin hydrochloride with the tetracycline antibiotic doxycycline. Developed by researchers at the Sidney Kimmel Cancer Center at Thomas Jefferson University, the regimen is being evaluated as a "window-of-opportunity" treatment for patients with localized breast, uterine, and cervical cancers awaiting surgery. The strategy leverages the metabolic reprogramming of cancer cells; metformin inhibits mitochondrial complex I, while doxycycline inhibits mitochondrial biogenesis by targeting mitochondrial ribosomes. Together, they aim to disrupt the metabolic synergy between cancer cells and their microenvironment, specifically targeting biomarkers such as Caveolin-1 in fibroblasts and monocarboxylate transporters (MCT1, MCT4) to inhibit tumor growth and survival.
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