Gynecological malignancies constitute a rather significant health burden, worldwide, with an incidence rate of approximately 30.4 per 100,000 population. These cancers collectively account for substantial morbidity and mortality; Ovarian cancer continues to represent the most lethal gynecological cancer due to its typically delayed diagnosis. Endometrial cancer incidence is steadily rising, mainly due to the rising prevalence of obesity and metabolic syndrome. Last but not least, cervical cancer still accounts for a major cause of cancer-related death especially in low-income countries, despite preventability through HPV vaccination.

Over the past decade, therapeutic advances have undoubtedly reshaped gynecological cancers’ landscape. The introduction of PARP inhibitors in ovarian cancer management, as well as immune checkpoint inhibition in endometrial and cervical cancer has demonstrated meaningful survival benefit in selected populations. Nevertheless, resistance and/or limited durability of response underscore the unmet need for more effective, novel modalities.

Antibody-drug conjugates (ADCs) have recently emerged as one of the most promising targeted therapeutic classes, offering the precision of a monoclonal antibody combined with the cytotoxic potency of chemotherapy. Currently, the folate receptor alpha (FRα)-targeted Mirvetuximab Soravtansine, the tissue factor (TF)-targeted Tisotumab Vedotin, and the human epidermal growth factor receptor 2 (HER2)-targeted Trastuzumab Deruxtecan are FDA-approved for patients with ovarian, cervical, and HER2-positive gynecological cancers, respectively.

The present Research Topic aims to explore the rapidly evolving landscape of ADCs in gynecological malignancies, with emphasis on:

● Robust predictive biomarkers in order to guide patient selection

● Mechanistic insights including but not limited to distinct resistance pathways and unique safety profile

● Optimal sequencing in the light of limited, robust large-scale randomized data

● Emerging ADCs under clinical development.

We welcome the submission of original research articles, meta-analyses, systematic as well as narrative reviews, study protocols, and translational studies in order to highlight the expanding potential of ADCs in precision gynecologic oncology.

*Drs. Dana Chase, Michele Zanoni and Marco Cavaco have declared they have no conflicts of interest with this Research Topic.

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.

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Antibody-Drug Conjugates: Emerging therapeutic strategy for Gynecological Cancers