PDK1 and neoplasm: This suggests that activation of mTORC1 occurs downstream of the PI3K–PDK1–AKT cascade in tumours harbouring IDH1 mutations, supporting the notion that 2HG-mediated inhibition of KDM4A affects the stability of DEPTOR leading to mTOR activation independently of the PI3K/AKT/TSC1-2 pathway (Fig. 5).