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Fouad Y, Gomaa A, Esmat G. Letter to the Editor: Decoding intrahepatic cholangiocarcinoma through lactate metabolism - from cellular states to therapeutic targets. World J Gastroenterol 2026; 32(29): 118233 [DOI: 10.3748/wjg.118233]
World J Gastroenterol. Aug 7, 2026; 32(29): 118233 Published online Aug 7, 2026. doi: 10.3748/wjg.118233
Letter to the Editor: Decoding intrahepatic cholangiocarcinoma through lactate metabolism - from cellular states to therapeutic targets
Yasser Fouad, Ahmed Gomaa, Gamal Esmat
Yasser Fouad, Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia 19111, Egypt
Ahmed Gomaa, Department of Gastroenterology and Endemic Medicine, Fayoum University, Fayoum 19777, Egypt
Gamal Esmat, Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo 11562, Egypt
Gamal Esmat, Department of Research, Badr University, Cairo 12342, Egypt
Author contributions: Fouad Y conceptualised the idea; Fouad Y, Gomaa A, and Esmat G wrote and revised the manuscript.
Conflict-of-interest statement: All authors declared no conflict of interest.
Corresponding author: Yasser Fouad, MD, Professor, Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, El-Horria Street, Minia 19111, Egypt. yasser.abdallah@mu.edu.eg
Received: December 30, 2025 Revised: February 5, 2026 Accepted: February 12, 2026 Published online: August 7, 2026 Processing time: 202 Days and 13.7 Hours
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver cancer characterized by significant intratumoral heterogeneity and limited treatment options. In the recent issue of World Journal of Gastroenterology, Wu et al revealed that lactate metabolism (LM) is a key determinant of malignant cell states in ICC, extending beyond its traditional role as a metabolic byproduct. Distinct tumor subpopulations exhibit a gradient of lactate metabolic activity, defining a hierarchy linked to differentiation, plasticity, and clinical aggressiveness. High LM states correlate with stemness features, enhanced mitochondrial function, and immunosuppressive interactions within the tumor microenvironment. Mitochondrial regulators such as cytochrome c1 connect lactate utilization to oxidative phosphorylation and redox homeostasis. Deciphering ICC through LM provides a unifying framework for tumor stratification and reveals potential metabolic-immune therapeutic targets.
