SMYD3 and cancer: Previous reports showed that c-MYC regulates the transcription of cancer stemness genes and promotes chemoresistance, especially against 5-fluorouracil (5-FU).66 We previously performed an extensive characterization of SMYD3 function in mediating cancer cell sensitivity to chemotherapeutic drugs.5 Prompted by these data, we investigated the potential of EM127 as a sensitizing agent in chemoresistant patient-derived CRC-SCs within a combinatorial strategy involving 5-FU.