Recent Advances in Ovarian and Endometrial Cancers: Molecular Mechanisms and Targeted Therapies

Submission Deadline: 31 May 2026 View: 360 Submit to Special Issue

Guest Editors

Dr. Giuseppe Gullo

Email: gullogiuseppe@libero.it

Affiliation: Unit of Obstetrics and Gynecology, AOOR Villa Sofia Cervello, University of Palermo, Palermo, 90100, Italy

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Research Interests: IVF, endoscopy (laparoscopy, hysteroscopy), fetal medicine, PCOS, endometriosis, reproductive endocrinology

Prof. Pasquale Patrizio

Email: pxp612@med.miami.edu

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miller School of Medicine, Miami, FL, 33146, USA

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Research Interests: Fertility preservation in cancer patients, whole ovary cryopreservation, biobanking of gametes and reproductive tissues, fertility preservation guidelines for cancer patients, personalized reproductive care for oncology patients, multidisciplinary oncofertility collaboration

Prof. Vito Chiantera

Email: vito.chiantera@unipa.it

Affiliation: 1.Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, 90133, Italy. 

2.Unit of Gynecologic Oncology, National Cancer Institute, IRCCS, Fondazione "G. Pascale", Naples, 80131, Italy

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Research Interests: gynecological oncology, deep endometriosis treatment, pelvic neurosurgery for pelvic innervation disorders

Summary

Gynecologic malignancies, a heterogeneous group of female reproductive system tumors (including ovarian, endometrial, cervical, vaginal, and vulvar cancer), are the second most commonly diagnosed female cancers worldwide.

Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes.

Endometrial cancer is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. The disease's pathogenesis involves several molecular mechanisms, such as genetic mutations, defects in the DNA mismatch repair (MMR) pathway, hormonal signaling pathway imbalances, epigenetic changes, and disturbances in angiogenesis.

At present, there are several candidate drugs targeting epigenetically modified enzymes, typically DNA methyltransferase inhibitors (DNMTis) and histone deacetylase inhibitors (HDACis), entering clinical research, potentially providing new treatment approaches for patients with gynecologic cancers.

Recent research has focused on the microRNAs (miRNAs) that have drawn substantial interest in EC, from diagnostics and pathophysiology to therapeutics. miRNA-related epigenetic mechanisms can be summarized in three patterns: miRNAs have the ability to directly bind to and silence target genes, serving as oncomiRNAs or tumor suppressors.

Furthermore, increased microvessel density (MVD) is positively correlated with aggressive phenotypes of the tumor. The association between angiogenesis and estrogen signaling is a distinctive feature of EC, in addition to alterations of traditional angiogenic biomarkers in other tumors, including vascular endothelial growth factor (VEGF) and its receptors, hypoxia-inducible factor-1α (HIF-1α), fibroblast growth factor (FGF), and other angiogenic factors.

EOCs (Epithelial Ovarian Cancer) are typically strongly vascularized, and the peritoneal vasculature is thick towards carcinomatosis, while the arterial circulation is poor, which accelerates the development of edema and inflammation. As the major subset of stromal cells in a number of human malignancies, cancer-associated fibroblasts (CAFs) can contribute to vascular stabilization in EOCs. CAFs promote angiogenesis through activation of the tumor-derived proangiogenic growth factors, platelet-derived growth factor (PDGF), VEGF, FGF, and transforming growth factor-beta (TGF-β), and by secreting stromal cell-derived factor-1 (SDF-1), which draws endothelial progenitor cells to the tumor stroma.

Recently, high-throughput sequencing of DNA has been successfully applied to several cancers, enabling the discovery of cancer genes and network-attacking mutations that can possibly translate into advances in cancer diagnosis and treatment.

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