TY - JOUR
T1 - Repositioning metformin in cancer
T2 - Genetics, drug targets, and new ways of delivery
AU - Aldea, Mihaela
AU - Craciun, Lucian
AU - Tomuleasa, Ciprian
AU - Berindan-Neagoe, Ioana
AU - Kacso, Gabriel
AU - Florian, Ioan Stefan
AU - Crivii, Carmen
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Chemoembolization
KW - Genetic
KW - Metformin
KW - Nanoparticle
KW - Stem
UR - http://www.scopus.com/inward/record.url?scp=84904751500&partnerID=8YFLogxK
U2 - 10.1007/s13277-014-1676-8
DO - 10.1007/s13277-014-1676-8
M3 - Review article
C2 - 24504677
AN - SCOPUS:84904751500
SN - 1010-4283
VL - 35
SP - 5101
EP - 5110
JO - Tumor Biology
JF - Tumor Biology
IS - 6
ER -