Correction: Recent therapeutic advances in gynecologic oncology: evolving roles of immunotherapy, antibody–drug conjugates, and clinical trial innovations

The occurrence of gynecologic cancers impacting the female reproductive system has been steadily rising, primarily due to modern lifestyle habits, unhealthy diets, and genetic predispositions [1]. These cancers encompass vulvar, uterine, vaginal, cervical, ovarian (OC), and fallopian-tube tumors, each classified according to anatomical origin. Fallopian-tube carcinoma remains exceptionally uncommon, accounting for less than 1% of female genital-tract malignancies [2,3]. In contrast, endometrial, ovarian, and cervical cancers are the most prevalent, together representing about 35-40% of cancers diagnosed in women worldwide [4]. Globally, cervical cancer ranks fourth among cancers in women, with approximately 604 000 new cases and 342 000 deaths in 2020, most occurring in low-and middle-income countries [5]. Endometrial (uterine) cancer is the sixth most common, causing roughly 417 000 cases and 97 000 deaths annually [6]. Ovarian cancer, often detected at advanced stages, ranks eighth, with 314 000 new cases and 207 000 deaths per year [7].Variations in incidence and mortality reflect access to screening, healthcare quality, reproductive behavior, and socioeconomic status [8]. These patterns underscore the global need for improved prevention, early detection, and individualized treatment strategies.The treatment of gynecologic cancers remains challenging, especially in advanced or recurrent disease [9]. Historically, carboplatin and paclitaxel have been the backbone of systemic therapy, acting through DNA cross-linking and microtubule stabilization, respectively [10]. However, resistance often develops due to enhanced DNA repair, survival-pathway activation, and altered drug metabolism [11]. Advances in molecular oncology and immunotherapy have revolutionized treatment paradigms by targeting tumor-specific mutations and immune-escape mechanisms. Agents such as bevacizumab (anti-angiogenic), PARP inhibitors (e.g., olaparib), and immune checkpoint inhibitors directed at PD-1/PD-L1 have become pivotal [12,13]. Bevacizumab received FDA approval in 2014 for ovarian cancer in platinum-resistant settings, while olaparib was first approved in 2014 for BRCA-mutated OC. Checkpoint inhibitors such as pembrolizumab were approved in 2017 for MSI-H or mismatch repair deficient (dMMR) solid tumors, including endometrial cancer. These therapies exemplify precision medicine by aligning treatment selection with molecular and immune biomarkers [14].Immune evasion constitutes a central obstacle to durable therapeutic response. The PD-1 receptor and its ligands PD-L1 and PD-L2 act as immune-checkpoint regulators that fine-tune T-cell activity and preserve peripheral tolerance (Figure 1) [15][16][17][18][19]. PD-L1 overexpression, observed in many gynecologic malignancies, enables tumor cells to bind PD-1 on activated T-cells and suppress immune cytotoxicity [18][19][20][21]. Blocking the PD-1/PD-L1 axis restores T-cell function, promotes tumor recognition, and enhances immune-mediated clearance [22]. High PD-L1 expression correlates with improved response to checkpoint blockade, establishing PD-L1 as a predictive biomarker for immunotherapy [23]. Ovarian, cervical, and endometrial cancers show frequent but variable PD-L1 expression [17].Ovarian cancers often display PD-L1 on both tumor cells and TAMs, whereas cervical tumors demonstrate high PD-L1 induction through HPV-related inflammation. Endometrial cancers, especially MSI-H or dMMR subtypes, exhibit strong PD-L1 expression associated with high T-cell infiltration. These differences influence responsiveness to PD-1 blockade and guide patient selection.Therapeutic antibodies targeting the PD-1/PD-L1 axis are primarily derived from IgG subclasses [24]. IgG1 antibodies can induce complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), while IgG4 variants minimize these effects [25]. The IgG format selection balances immunostimulatory potential with safety [26]. Pembrolizumab (IgG4) was approved in 2017 for PD-L1-positive cervical cancer, and dostarlimab (IgG4) in 2021 for dMMR endometrial cancer, emphasizing their therapeutic value in gynecologic oncology.Recent years have seen a paradigm shift toward immune-based and biologically informed treatments. Pivotal trials-SHAPE, INTERLACE, KEYNOTE-A18, BEATcc, COMPASSION-16, NRG-GY018, RUBY, AtTEnd, DUO-E, LMS-04, PRIMA, DUO-O, ATHENA-combo, and FIRST-ENGOT-OV44-have redefined management across cervical, endometrial, and ovarian cancers [27,28]. Maintenance and combination regimens now incorporate PARP inhibitors, anti-angiogenic agents, and ICIs for improved survival and quality of life. The approval of niraparib (2019) as first-line maintenance in OC and lenvatinib plus pembrolizumab (2021) for advanced endometrial cancer set new standards of care. The DESTINY-PanTumor02 basket trial further validated trastuzumab deruxtecan for HER2-positive tumors, including gynecologic types. Molecular profiling and biomarker-guided stratification have enhanced precision oncology [27,28]. Trastuzumab deruxtecan, approved in 2022 for HER2-positive solid tumors irrespective of tissue origin, exemplifies antibody-drug conjugates (ADCs) transforming gynecologic oncology [18].Collectively, these developments mark a transition from conventional chemotherapy to biomarkerdriven immunotherapy and ADC approaches. The ongoing priorities are optimizing combination regimens, mitigating resistance, and extending these innovations to diverse histologic subtypes [19,29]. This review therefore examines current therapeutic advances in gynecologic oncology, emphasizing immunotherapy and ADC platforms that improve progression-free survival and reduce systemic toxicity in both early-stage and advanced disease.This narrative review followed a structured and transparent literature search to ensure clarity, reproducibility, and comprehensive coverage of recent advances in gynecologic oncology. The main goal was to examine recent progress in systemic therapy, focusing on immunotherapy and ADCs. A structured search strategy was designed that included database selection, keyword definition, and specific inclusion and exclusion criteria (Fig. 2). The process consisted of four phases: initial search, screening, eligibility assessment, and final inclusion. These stages were applied to identify peer-reviewed studies relevant to immunotherapy, ADCs, and targeted therapies in cervical, endometrial, and ovarian cancers. A total of 939 records were collected from PubMed, Scopus, Web of Science, ScienceDirect, Google Scholar, JSTOR, Science.gov, and the Bielefeld Academic Search Engine (BASE). After removing duplicates and unrelated records, 745 studies were reviewed by title, and 455 were evaluated by abstract and full text. In the final stage, 142 publications met the eligibility criteria and were included in the qualitative synthesis. Among these, 38 references were used to provide background information and methodological justification, while 104 supported the main analysis of therapeutic evidence and clinical outcomes.The search was conducted in February 2025 using combinations of the following keywords and Boolean operators: gynecologic oncology, cervical cancer, endometrial cancer, ovarian cancer, immune checkpoint inhibitors, PD-1, PD-L1, antibody-drug conjugates, trastuzumab deruxtecan, clinical trials, targeted therapy, and novel therapies. Only English-language, peer-reviewed publications from 2010 to 2025 were included. Editorials, letters, brief communications, and purely theoretical studies were excluded. Two independent reviewers evaluated each study for relevance and quality, and disagreements were resolved by consensus.ADCs have surfaced as a promising therapeutic approach in gynecologic oncology by selectively delivering potent cytotoxic agents to tumor cells while limiting off-target toxicity. In cervical cancer, the ADC tisotumab vedotin (TV) targeting tissue factor (TF) has gained FDA approval based on the innovaTV 204 trial, which showed durable responses in patients with recurrent or metastatic disease after standard chemotherapy failure. In endometrial cancer, agents such as trastuzumab deruxtecan targeting HER2 are under active investigation, especially in tumors with HER2 overexpression [30].Preliminary studies suggest these ADCs may work synergistically with immune checkpoint inhibitors in biomarker-selected subtypes of endometrial In which receptor has clinical in on from the trial, ADC received FDA approval and is under in combination regimens gynecologic malignancies, current ADCs in and types. and the while and are cytotoxic most agents are conjugates with These in both approved and underscore the of molecular profiling and tumor-specific expression in optimizing ADC cervical cancer, classified as stages tumors to the with and have at these The standard treatment has been a associated with including and by in less than 1% of tumors less has been to reduce trial, a with in early-stage disease or Among was for for and that is in patients the and these were evidence from the trial showed and survival for emphasizing that approach and patient selection The study further that can in disease and the current toward less in early-stage cervical to the therapeutic in cervical cancer is toward informed and immune-based checkpoint inhibitors such as pembrolizumab and ADCs have responses in recurrent and metastatic and are in or combination with targeted agents such as bevacizumab and PARP inhibitors may and of response. these disease stages the need for or In contrast, the trial evaluated in women with tumors, and a and in patients from including and demonstrate a shift toward individualized and less in early-stage cervical cancer the safety of in while validated as to full the of and evidence for approaches. 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