The Tumor Microenvironment as a Driver of Disease Progression and Therapeutic Response in Gynecological Malignancies
Key Insights
The tumor microenvironment (TME) plays a critical regulatory role in gynecological cancer progression, shaping metastatic potential and treatment outcomes through complex interactions between malignant cells and surrounding stromal, immune, vascular, and extracellular matrix components.
Ovarian, endometrial, and cervical cancers each exhibit distinct TME features driven by factors such as stromal remodeling, hypoxia, hormonal regulation, inflammation, and viral oncogenesis, contributing to therapeutic resistance.
Recent advances in spatial profiling, single-cell analyses, and organoid-based modeling now enable unprecedented resolution in studying the gynecological TME, opening avenues for TME-informed therapeutic strategies.
The tumor microenvironment (TME) 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. With recent advances in spatial profiling, single-cell analyses, and organoid-based modeling, the gynecological TME can now be studied with unprecedented resolution, deepening biological understanding and guiding the development of TME-informed therapeutic strategies.
Distinct TME Features Across Gynecological Cancers
In ovarian cancer (search), stromal remodeling, hypoxia, abnormal vasculature, and vascular mimicry contribute to aggressive disease behavior and therapeutic resistance. Endometrial and cervical cancers, by contrast, exhibit distinct TME features driven by hormonal regulation, inflammation, and viral oncogenesis. These cancer-specific TME characteristics underscore the need for tailored therapeutic approaches that account for the unique biology of each malignancy.
Key Drivers of Progression and Resistance
TME-driven processes — including stromal activation, immune suppression, extracellular matrix remodeling, aberrant angiogenic signaling, and vascular mimicry — significantly contribute to the challenges of disease heterogeneity, rapid onset of treatment resistance, and limited benefit from current targeted or immunotherapeutic strategies. Many gynecological cancers present with substantial heterogeneity and respond poorly to existing therapies, making TME-directed interventions a promising avenue for therapeutic development.
Advancing Precision Oncology Through TME Research
This Research Topic, led by Topic Editors Dr. Fabian Kraus, Dr. Adelina Silvana Gheorghe, and Prof. Dana Stanculeanu, aims to address the critical need for deeper mechanistic insight into how the TME drives disease progression and therapeutic response. The collection welcomes Original Research, Reviews, Mini-reviews, Clinical studies, Methodological papers, and Perspectives focused on the tumor microenvironment in gynecological cancers.
Relevant themes include immune landscape characterization and immune evasion, stromal and fibroblast-driven remodeling, extracellular matrix composition and signaling, tumor vasculature and vascular mimicry, hypoxia and metabolic reprogramming, spatial and single-cell profiling approaches, TME-mediated therapeutic resistance and biomarker discovery, TME-targeted or vasculature-directed therapeutic strategies, and novel model systems such as organoids, ex vivo cultures, and engineered microenvironments.
By highlighting pathways that can serve as predictive biomarkers or therapeutic targets, the Research Topic seeks to advance precision oncology approaches and foster the development of more effective, personalized treatments for patients with gynecological cancers. Manuscripts are expected to present clear conclusions and highlight how the findings advance understanding of the gynecological tumor microenvironment and its implications for improving patient outcomes.
Disclosures
Dr. Fabian Kraus received funding from the German Research Foundation and participated in the GynOnco Barcamp hosted by AstraZeneca. Dr. Adelina Silvana Gheorghe serves as Vice-President of ARCOF (Romanian Association for Women's Cancer Research) and is a Gilead grant recipient. Prof. Dana Stanculeanu serves as President of the Romanian Association for Women's Cancers Research.