AKT1 and osteosarcoma: Therefore, in this review, we focus on the key mechanisms involved in resistance to chemotherapy in osteosarcoma CSCs, namely, detoxification systems (drug efflux transport and ALDH), survival-related pathways (ERK, AKT), adaptive metabolic routes, altered cell cycle and DNA repair, enhanced apoptosis and modulation of the tumor microenvironment (hypoxia, inflammation), by giving appropriate examples.