SIRT6 and neoplasm: The main mechanisms include: (a) Overexpression of the hypoxia-inducible factor HIF-1α; (b) Activation of oncogenes (e.g., c-Myc, mTORC1, Akt, and Ras); (c) Inactivation of tumor suppressors (e.g., p53 mutation); (d) Activation of signaling pathways such as receptor tyrosine kinase-PI3K-Akt-mTORC1 and Jak-Stat3; (e) Inactivation of the LKB1-AMPK signaling pathway; (f) Downregulation/loss of function of several miRNAs and SIRT3, SIRT6, etc.; and (g) Interaction with the hostile tumor microenvironment and cancer-associated stromal cell interactions [18].