An anti-neoplastic tale of metformin through its transport
Abstract
Metformin is an attractive candidate drug among all the repurposed drugs for cancer. Extensive preclinical and clinical research has evaluated its efficacy in cancer therapy, revealing a mixed outcome in clinical settings. To fully exploit metformin's therapeutic potential, understanding cellular factors relevant to its transport and accumulation in cancer cells needs to be understood. This review highlights the relevance of metformin transporter status towards its anti-cancer potential. Metformin transporters are regulated at pre-transcriptional, transcriptional, and post-translational levels. Moreover, the tumour microenvironment can also influence metformin accumulation in cancer cells. Also, Metformin treatment can regulate its transporters by altering global DNA methylation, protein acetylation, and transcription factors. Importantly, metformin transporters not only influence chemotherapeutic drug toxicity but are also associated with the prognosis and survival of individuals having cancer. Strategic decisions based on the expression and regulation of metformin transporters holds promise for its therapeutic implications and relevance.
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