Indeed, when cancer cells were treated with chemotherapeutic agents that are currently administered to CRC patients and whose activity has been shown to involve FOXO3a in cellular models, such as cisplatin, irinotecan, 5-FU and etoposide [91,109,117,118,119], mitochondrial FOXO3a (mtFOXO3a) was required for mitochondrial function preservation, chemotherapy resistance and cell survival in a MEK/ERK-dependent manner (Figure 2). The gene discussed is FOXO3; the disease is colorectal carcinoma.