Stromal and Metabolic Drivers of the Tumor Microenvironment in Colorectal Cancer

Colorectal cancer (CRC) ranks among the most prevalent and lethal malignancies worldwide, with disease progression shaped not only by tumor cell-intrinsic genetics but by the dynamic architecture of the surrounding tumor microenvironment (TME). While immune-mediated mechanisms have dominated the TME conversation over the past decade, a rapidly growing body of evidence highlights the equally critical, and largely untargeted, roles of stromal, metabolic, and non-immune regulatory processes in driving invasion, metastasis, therapeutic resistance, and disease recurrence. Cancer-associated fibroblasts (CAFs), endothelial cells, pericytes, adipocytes, and enteric neurons engage in complex paracrine networks with tumor cells through extracellular matrix remodeling, metabolic substrate competition, and mechanical signaling, collectively shaping a permissive microenvironment that remains incompletely understood.This Research Topic seeks to consolidate and advance knowledge on the non-immune TME in CRC, with a particular focus on stromal cell biology, metabolic crosstalk, ECM dynamics, vascular remodeling, and the broader landscape of non-immune cellular interactions. We invite contributions spanning basic science, translational research, and clinical studies across primary tumors and metastatic CRC, including liver and peritoneal settings where stromal influence is especially pronounced.To capture the breadth and depth of current research, we welcome articles including but not limited to the following topics:• CAF subtypes, plasticity, and heterogeneity and their roles in CRC growth, drug resistance, and desmoplastic remodeling.• Metabolic reprogramming within the CRC TME, including nutrient competition, lipid oxidation, lactate shuttling, and amino acid crosstalk between tumor and stromal compartments.• ECM composition, matrix stiffness, and remodeling enzymes (MMPs, LOX family) as regulators of CRC invasiveness and distant metastasis.• Tumor vasculature, angiogenesis, and hypoxia-driven signaling and their effects on stromal behavior, drug penetration, and disease progression.• Non-immune stromal cell interactions involving adipocytes, pericytes, enteric neurons, and mesenchymal populations within the CRC niche.• Epithelial-mesenchymal transition dynamics driven by stromal paracrine signals, TGF-β signaling, and metabolic cues in CRC.We invite researchers from oncology, molecular biology, gastroenterology, and translational medicine to join this collection and help define the next generation of non-immune, stromal-targeted strategies in colorectal cancer. Please 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: Claudia Gentili, Héctor R Contreras, JULIANA SESMA, Jean-Pierre Raufman Source: https://www.frontiersin.org/research-topics/83234/stromal-and-metabolic-drivers-of-the-tumor-microenvironment-in-colorectal-cancer