Figure 2.

A three-pronged therapeutic approach to target three major tumor cell subpopulations. Proliferating, differentiated tumor cells may be targeted with classical cytotoxic drugs or with antibody-drug conjugates. Tumor cells that come in contact with cytotoxic drug concentrations that are subcytotoxic may respond to this stress by undergoing EMT or autophagy (thick lines). mTOR inhibitors are a second class of drugs that may act preferentially on EMT tumor cells, inducing them to undergo autophagy (thick line). Autophagic cells may be induced toward demise by a third class of drugs, inducers of autophagic cell death (autosis). This therapeutic scheme is expected to act on the three major tumor cell populations leading to their demise and avoiding them to accumulate in one of the two resistant compartments (i.e., EMT or autophagic tumor cells) as a consequence of genotoxic stress.