SETD2 and neoplasm: At present, it is believed that the Warburg effect does not arise from mitochondrial dysfunction in tumor cells, but from the synergy of overexpression of hypoxia-inducible factor-1 (HIF-1), activation of oncogenes (KRAS, c-MYC), loss of tumor suppressors (mutant P53, PTEN, microRNAs), activation of signaling pathways, the TME, and epigenetic modifications (Vaupel and Multhoff, 2021).