Figure 1. AKT-MTOR and autophagy triple targeting as an effective antitumoral therapy in MCL. Treatment with AKTi-1/2, an isoselective AKT inhibitor, prevents AKT rephosphorylation upon everolimus-mediated inhibition of MTORC1, thus enhancing the activity of the rapalog in MCL cells. However, the degree of autophagy induced by dual MTOR-AKT inhibition determines the fate of the cells, which can undergo either apoptotic cell death or survival. In low-responsive everolimus-AKTi-1/2 MCL cells, pro-survival autophagy can be counteracted by autophagy inhibitors such as bafilomycin A₁ (Baf. A1) or hydroxychloroquine (HCQ), thus restoring the cytotoxic potential of MTOR-AKT targeting.