From Dissipative Tumor Ecosystems to Clinical Translation: Targeting Tumor Acidity and Metabolic Reprogramming in Advanced Solid Tumors

Cancer is increasingly recognized as a dynamic, open, non-equilibrium biological system rather than simply a collection of malignant cells. Continuous interactions among cancer cells, stromal cells, immune cells, the vasculature, and the extracellular environment create a self-organizing tumor ecosystem in which metabolic reprogramming, extracellular acidification, inflammation, and therapeutic resistance emerge as interconnected phenomena. From this perspective, the concept of dissipative structures provides a valuable theoretical framework for understanding tumor biology without implying support for any specific therapeutic strategy.One of the defining characteristics of this tumor ecosystem is extracellular acidity, driven largely by the Warburg effect, lactate production, altered proton transport, and dysregulated pH homeostasis. An acidic tumor microenvironment contributes to invasion, metastasis, immune evasion, angiogenesis, and resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Recent advances have identified multiple mechanisms regulating tumor acidity, including NHE1, MCT1/4, carbonic anhydrases, bicarbonate transporters, and metabolic pathways that collectively shape tumor progression.At the same time, increasing attention has been directed toward translating these biological insights into clinical practice. Novel approaches including metabolic intervention, buffering strategies, dietary modification, pH-targeted therapies, biomarker development, functional imaging, and rational combinations with standard anticancer treatments are being actively investigated.This Research Topic aims to bring together basic, translational, and clinical studies that advance our understanding of tumor acidity and metabolic reprogramming within the broader context of tumor ecosystem biology. We particularly welcome interdisciplinary contributions integrating cancer metabolism, tumor microenvironment research, systems biology, immunology, pharmacology, imaging, biomarker development, and clinical oncology.Topics of interest include, but are not limited to:• Tumors as open, non-equilibrium biological systems and dissipative structures• Cancer metabolism, the Warburg effect, lactate biology, and pH regulation• Acidic tumor microenvironment, immune modulation, invasion, metastasis, and therapeutic resistance• Molecular mechanisms regulating tumor acidity, including NHE1, MCT transporters, carbonic anhydrases, and related pathways• Biomarkers and imaging of tumor acidity and systemic acid-base status• Metabolic interventions, buffering strategies, dietary approaches, and pH-targeted therapies• Combination strategies integrating metabolic modulation with chemotherapy, radiotherapy, targeted therapy, or immunotherapy• Translational and clinical studies investigating therapeutic modulation of tumor acidity in advanced solid tumorsPlease note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Reo Hamaguchi, Hiromi Wada, Haruka Handa Source: https://www.frontiersin.org/research-topics/85858/from-dissipative-tumor-ecosystems-to-clinical-translation-targeting-tumor-acidity-and-metabolic-reprogramming-in-advanced-solid-tumors