The underlying mechanisms of CSCs in CRC attributed to therapy resistance include, the activation of growth signalling pathways such as Hedgehog, Notch, TGF- β, Wnt/β-catenin, Hippo, PI3/AKT etc., the dysregulation of microRNAs, acquisition of quiescent state, metabolic switch, phenotypic plasticity etc. (Figure 1). The gene discussed is AKT1; the disease is colorectal carcinoma.