RB1 and colorectal carcinoma: As has been observed in other types of cancer24–29, the cytostatic effect of metformin on CRC cells is due to a reduction in cell proliferation, an increased accumulation of cells in the G0/G1 phase, a decrease in the expression of proteins controlling cell cycle progression such as cycD1 and c-Myc, and the inhibited phosphorylation of the cyclin D1 target pRb.