title: Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery.
abstract: After sitting many years on the shelves of drug stores as a harmless antidiabetic drug, metformin comes back in the spotlight of the scientific community as a surprisingly effective antineoplastic drug. Metformin targets multiple pathways that play pivotal roles in cancer progression, impacting various cellular processes, such as proliferation, cell death, metabolism, and even the cancer stemness features. The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin's anticancer efficiency. This could indicate a need for tumor genetic profiling in order to identify patients most likely to benefit from metformin treatment. Considering that the majority of experimental models suggest that higher, supra-clinical doses of metformin should be used in order to obtain an antineoplastic effect, new ways of drug delivery could be developed, such as metformin-loaded nanoparticles or incorporation of metformin into microparticles used in transarterial chemoembolization, with the aim of obtaining higher intratumoral drug concentrations and a targeted therapy which will ultimately maximize metformin's efficacy.
authors: Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Str, Cluj-Napoca, 400337, Romania, mihaela.aldea1@gmail.com.
authors: Mihaela
authors: M
authors: Aldea
authors: Lucian
authors: L
authors: Craciun
authors: Ciprian
authors: C
authors: Tomuleasa
authors: Ioana
authors: I
authors: Berindan-Neagoe
authors: Gabriel
authors: G
authors: Kacso
authors: Ioan Stefan
authors: IS
authors: Florian
authors: Carmen
authors: C
authors: Crivii
mesh_terms: D000818:Animals; D016461:Chemoembolization, Therapeutic; D006801:Humans; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D009154:Mutation; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*; D027701:Organic Cation Transport Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D027701:Organic Cation Transport Proteins; D011518:Proto-Oncogene Proteins; D008687:Metformin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins