PTEN and malignant glioma: Specifically, the high expression of Smurf1 in malignant gliomas promotes the hyperactivation of the mTORC1 pathway by ubiquitin‐mediated degradation of PTEN.[34, 35] The phosphorylation of p62 mediated by mTORC1 competitively binds to Keap1 (Kelch‐like ECH‐associated protein 1), a negative regulator of the antioxidant transcription factor Nrf2.[36, 37] The ability of cells to rebalance the homeostasis of the intracellular environment by activating lysosomal autophagy in response to stress perturbations is a key driving force for tumor drug resistance.