Oral cancer tumors occur in the mouth and are mainly derived from oral mucosa linings. It is one of the most common and fatal malignant diseases worldwide. The intratumor heterogeneity (ITH) of oral cancerous tumor is vast, so it is challenging to study and interpret. Due to environmental selection pressures, ITH arises through diverse genetic, epigenetic, and metabolic alterations. The ITH also talks about peri-tumoral vascular/ lymphatic growth, perineural permeation, tumor necrosis, invasion, and clonal expansion/ the coexistence of multiple subclones in a single tumor. The heterogeneity offers tumors the adaptability to survive, induce growth/ metastasis, and, most importantly, escape antitumor therapy. Unfortunately, the ITH is prioritized less in determining disease pathology than the traditional TNM classifications or tumor grade. Understanding ITH is challenging, but with the advancement of technology, this ITH can be decoded. Tumor genomics, proteomics, metabolomics, and other modern analyses can provide vast information. This information in clinics can assist in understanding a tumor's severity and be used for diagnostic, prognostic, and therapeutic decision-making. Lastly, the oral tumor ITH can lead to individualized, targeted therapy strategies fighting against OC.
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