Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.