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In the present review, we have inventoried the genes involved in the lack of CRC response to pharmacological treatment, classifying them into seven groups (from MOC-1 to MOC-7) according to functional criteria to identify cancer cell weaknesses. This classification will be useful to pave the way for developing sensitizing tools consisting of (i) new agents to be co-administered with the active drug; (ii) pharmacological approaches, such as drug encapsulation (e.g., into labeled liposomes or exosomes); (iii) gene therapy interventions ai