The Tumor Microenvironment as a Driver of Disease Progression and Therapeutic Response in Gynecological Malignancies

The tumor microenvironment has emerged as a major regulator of cancer progression across solid tumors, but its influence is particularly pronounced in gynecological malignancies. These cancers display complex interactions between malignant cells and their surrounding immune, stromal, vascular, and extracellular matrix components, all of which shape metastatic potential and treatment outcomes. In ovarian cancer, for example, stromal remodeling, hypoxia, abnormal vasculature, and vascular mimicry contribute to aggressive disease behavior and therapeutic resistance. Endometrial and cervical cancers exhibit distinct TME features driven by hormonal regulation, inflammation, and viral oncogenesis.With recent advances in spatial profiling, single-cell analyses, and organoid-based modeling, the gynecological TME can now be studied with unprecedented resolution. This Research Topic aims to leverage these innovations to deepen biological understanding and guide the development of TME-informed therapeutic strategies.The goal of this Research Topic is to address the critical need for deeper mechanistic insight into how the tumor microenvironment (TME) drives disease progression and therapeutic response in gynecological malignancies. Many of these cancers present with substantial heterogeneity, rapid onset of treatment resistance, and limited benefit from current targeted or immunotherapeutic strategies. TME-driven processes—including stromal activation, immune suppression, extracellular matrix remodeling, aberrant angiogenic signaling, and vascular mimicry—significantly contribute to these challenges and represent promising avenues for therapeutic development.This collection seeks to integrate mechanistic, translational, and early clinical research to uncover TME-mediated determinants of tumor aggressiveness and therapy response. By highlighting pathways that can serve as predictive biomarkers or therapeutic targets, the Research Topic aims to advance precision oncology approaches and foster the development of more effective, personalized treatments for patients with gynecological cancers.This Research Topic welcomes Original Research, Reviews, Mini-reviews, Clinical studies, Methodological papers, and Perspectives focused on the tumor microenvironment in gynecological cancers. Relevant themes include, but are not limited to:• Immune landscape characterization and immune evasion• Stromal and fibroblast-driven remodeling• Extracellular matrix composition, stiffness, and signaling• Tumor vasculature, endothelial–tumor interactions, and vascular mimicry• Hypoxia, metabolic reprogramming, and angiogenic signaling• Spatial and single-cell profiling approaches• TME-mediated therapeutic resistance and biomarker discovery• TME-targeted or vasculature-directed therapeutic strategies• Novel model systems such as organoids, ex vivo cultures, and engineered microenvironmentsManuscripts should present clear conclusions and highlight how the findings advance understanding of the gynecological tumor microenvironment and its implications for improving patient outcomes.TE Dr. Fabian Kraus received funding from the German Research Foundation and participated in the GynOnco Barcamp hosted by AstraZenecaTE Dr. Adelina Silvana Gheorghe is Vice-President of ARCOF (Romanian Association for Womens Cancer Research), and is a Gilead grant recipientTE Prof. Dana Stanculeanu is President of Romanian Association for Womens' Cancers Research Topic editors: Fabian Bernhard Thaddäus Kraus, Adelina Silvana Gheorghe, Dana Lucia Stanculeanu Source: https://www.frontiersin.org/research-topics/76464/the-tumor-microenvironment-as-a-driver-of-disease-progression-and-therapeutic-response-in-gynecological-malignancies