Tumor Ecosystem Remodeling and Therapeutic Resistance in Solid Tumors: Mechanisms, Patient-Derived Models and Translational Vulnerabilities

The study of the tumor ecosystem has progressed notably in recent years as cancer research shifts from a cell-intrinsic to a multi-compartmental perspective. Solid tumors are now recognized as dynamic ecosystems in which complex interactions among malignant cells, stromal components, immune infiltrates, the extracellular matrix, and vascular and metabolic niches collectively shape treatment outcomes. While early investigations centered primarily on genetic mutations driving tumorigenesis, newer studies reveal that therapeutic efficacy and resistance are profoundly influenced by non-genetic and microenvironmental factors. Recent single-cell and spatial multi-omic studies have illuminated how therapy-induced plasticity, tumor–stroma communication, and immune landscape remodeling determine treatment response. However, despite these advances, a unified understanding of how therapeutic interventions actively reshape tumor ecosystems and sustain resistant cell states remains incomplete. Addressing this gap requires integrating mechanistic biological studies with functionally relevant patient-derived models that more accurately capture the complexity and evolution of human tumors under therapeutic pressure.This Research Topic aims to foster an integrative understanding of how dynamic remodeling of the tumor ecosystem drives response and resistance to diverse therapeutic modalities in solid tumors. It seeks to answer key questions regarding the cellular and molecular determinants that govern adaptive responses, the emergence of residual disease, and eventual relapse. By emphasizing studies that uncover the mechanisms of tumor plasticity, stromal and immune reprogramming, and therapy-induced ecosystem transitions, this collection strives to identify actionable vulnerabilities that can inform new therapeutic strategies. The overarching goal is to bridge mechanistic insights and clinical translation by highlighting how innovative tumor models and advanced omics technologies can illuminate resistance pathways and refine patient treatment strategies.To gather further insights into tumor ecosystem dynamics and their impact on treatment outcomes in solid tumors, we welcome articles addressing, but not limited to, the following themes:o Tumor ecosystem remodeling under therapeutic pressure in solid tumors.o Mechanisms of chemotherapy, radiotherapy, targeted therapy, endocrine therapy, and immunotherapy resistance.o Tumor cell plasticity, epithelial–mesenchymal transition, stem-like states, dormancy, and lineage reprogramming.o Fibroblast/CAF-associated programs, extracellular matrix remodeling, and stromal regulation of treatment response.o Immune microenvironment remodeling and immune escape during therapy.o Metabolic adaptation and microenvironmental stress responses associated with therapeutic resistance.o Single-cell, spatial, transcriptomic, epigenomic, and multi-omics approaches to dissect tumor ecosystem dynamics.o Patient-derived organoids, xenografts, tumor slices, co-culture systems, and organ-on-chip models.o Functional drug screening and perturbation-based strategies using patient-derived models.o Translational vulnerabilities, biomarkers, and rational combination therapies to overcome therapeutic resistance. Topic editors: Xinxin Rao, Wenzhi Shen, Tongchao Jiang Source: https://www.frontiersin.org/research-topics/83803/tumor-ecosystem-remodeling-and-therapeutic-resistance-in-solid-tumors-mechanisms-patient-derived-models-and-translational-vulnerabilities