TP53 and neoplasm: The phenomenon of perineural invasion (PNI), representing cancer invasion in or around or penetrate nerve or route for cancer metastasis, is correlated with poor cancer prognosis.31,110 PNI has been reported in multiple cancers, such as those in the head and neck, pancreas, prostate, breast, colon, and ovaries.28,30,110,113 Amit et al.114 showed that oral cavity squamous cell carcinoma cancer cells with loss of TP53 can reprogram tumor-associated neurons to adrenergic phenotype depending on the signal transduction of EVs, which further promotes tumor progression.