The Microenvironment and Beyond: Novel Targets in Gynecologic Malignancies

The tumor microenvironment (TME) is increasingly recognized as a dynamic determinant of progression, metastasis, and therapeutic resistance in gynecologic malignancies. This complex ecosystem—comprising immune cells, cancer-associated fibroblasts, vasculature, and extracellular matrix—can limit treatment efficacy while also offering therapeutic opportunities. Moving beyond an exclusive focus on canonical tumor-intrinsic drivers, an important research frontier involves targeting the crosstalk between tumor cells and their surrounding milieu.This Research Topic seeks to highlight the pivotal role of the TME, alongside other emerging, non-canonical targets, in reshaping the treatment landscape for ovarian, endometrial, cervical, and other gynecologic cancers. We aim to curate a collection of research examining how therapeutic strategies directed at the TME and related pathways may overcome resistance and improve patient outcomes. By focusing on the ecosystem that sustains tumors, this Research Topic will help inform the development of multi-targeted, combinatorial therapies.The aim of this Research Topic is to provide a dedicated platform for advances in understanding and therapeutically exploiting the tumor microenvironment and other novel biological targets in gynecologic cancers. We welcome submissions that dissect the components of the TME, elucidate their pro-tumorigenic functions, and translate these insights into innovative therapeutic strategies.The scope of this Research Topic includes, but is not limited to, the following themes:• The Cellular TME: Investigations into the role and targeting of tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), tumor-infiltrating lymphocytes (TILs), and myeloid-derived suppressor cells (MDSCs).• The Physical and Soluble TME: Research focusing on the extracellular matrix (ECM), stiffness, hypoxia, angiogenesis, and key chemokine/cytokine networks.• Metabolic Crosstalk: Studies exploring metabolic adaptations and dependencies of tumor and stromal cells within the TME.• Mechanisms of Resistance: Elucidating how the TME confers resistance to conventional chemotherapy, radiotherapy, and targeted agents.• Beyond the TME: Discovery and validation of other novel targets, including neoantigens, oncogenic viruses, non-coding RNAs, and epigenetic regulators.• Biomarkers and Patient Stratification: Identification of TME-based biomarkers (e.g., spatial transcriptomics, multiplex immunohistochemistry) to predict response to therapy.• Combination Therapies: Preclinical and clinical studies on rational combinations of TME-targeting agents with immunotherapy, targeted therapy, or standard-of-care treatments.• Translation to Clinical Practice: Reports from clinical trials evaluating novel agents that target the TME or other emerging pathways.Therapeutic Targeting of the TME: o Strategies to re-educate the immune landscape (e.g., overcoming T-cell exhaustion) o Agents targeting CAF activation, ECM remodeling, or angiogenesis o Novel drug delivery systems designed to penetrate and modulate the TMEWe invite submissions that advance understanding of the TME and other emerging targets and that open new avenues for treating gynecologic malignancies.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: Erum Dilshad, Haifeng Qiu Source: https://www.frontiersin.org/research-topics/77727/the-microenvironment-and-beyond-novel-targets-in-gynecologic-malignancies