Targeting the Epigenetic-Metabolic Axis in the Tumor Microenvironment: How Oncometabolites Reprogram the Molecular Landscape of Cancer?

Muzamil Hussain — Sun, 11 Oct 2026 00:00:00 +0000

The traditional perspective views cancer as epigenetic disease. However, this review highlights the dynamic interplay between epigenetics and metabolism, where oncometabolites reshape the molecular architecture of the tumor microenvironment (TME). We explore how mutations in tricarboxylic acid (TCA) cycle enzymes (IDH, SDH, FH) or stress-induced metabolic reprogramming lead to the accumulation of metabolites such as D-2-hydroxyglutarate (D2HG), succinate, and fumarate. These oncometabolites act as competitive inhibitors of α-ketoglutarate–dependent dioxygenases, driving DNA hypermethylation, histone modifications, pseudohypoxia, and epitranscriptomic changes such as m6A methylation. Importantly, this crosstalk extends beyond cancer cells, reshaping immune function, promoting T-cell exhaustion via histone lactylation, and influencing ferroptosis. We also discuss emerging therapeutic strategies, including mutant IDH inhibitors, nanomedicine approaches, and AI-driven multi-omics, while acknowledging challenges posed by tumor heterogeneity and metabolic plasticity. Understanding the epigenetic–metabolic axis opens promising avenues for precision and translational oncology.

Phytochemical characterization of Irvingia gabonensis (Aubry-Lecomte Ex o’rorke) Balil seeds: Insights into its bioactive compounds and potential nutraceutical, pharmaceutical and cosmetic applications

Sun, 11 Oct 2026 00:00:00 +0000

The benefits of African mango Irvingia gabonensis extends beyond its culinary importance, it possesses remarkable phytochemical properties. This highlights the need for further biochemical analysis, hence the present study aimed to conduct an extensive phytochemical screening of I. gabonensis seed using GC-MS profiling. Mature fruits were obtained from Watt market, a local market in Calabar, and were manually de-pulped to extract the seeds. The seeds were air-dried under shade at room temperature (25–30°C) for 14–21 days. The dried seeds were ground into fine powder using a mortar and pestle. The powder was stored in airtight, amber containers at 4°C to prevent oxidation and degradation before extraction. Following standard protocols, a combination of qualitative and quantitative phytochemical screening techniques was employed to detect the presence of key bioactive compounds such as alkaloids, flavonoids, tannins, phenolics, and terpenoids. Bioactive compounds were extracted using Soxhlet extraction with analytical-grade methanol (99.9%) as the solvent. The extract was filtered and concentrated using a rotary evaporator at 40°C under reduced pressure to prevent thermal degradation. Phytochemical screening data were analyzed using mean ± standard deviation values for triplicate experiments. GC-MS data were evaluated using relative peak area (%) to determine the major bioactive constituents. Results indicate a strong presence of saponins, terpenoids, and moderate presence of flavonoid, alkaloids, and phenols. GC-MS chromatographic analysis revealed a complex chemical composition comprising 20 distinct chromatographic peaks, detected compounds exhibited retention times ranging from 4.070 to 22.869 min, reflecting differences in their chemical properties and molecular characteristics. Among detected peaks, Peak 4, with a retention time of 8.610 min, was the predominant constituent, accounting for 74.777% of the total chromatographic peak area. This study concludes that I. gabonensis seed extract is a valuable source of bioactive compounds with significant nutritional, therapeutic, and industrial potential.

PAKISTAN JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY

Targeting the Epigenetic-Metabolic Axis in the Tumor Microenvironment: How Oncometabolites Reprogram the Molecular Landscape of Cancer?

Phytochemical characterization of Irvingia gabonensis (Aubry-Lecomte Ex o’rorke) Balil seeds: Insights into its bioactive compounds and potential nutraceutical, pharmaceutical and cosmetic applications