Expert Review of Anticancer Therapy

Recent advances in photodynamic therapy combined with chemotherapy for cervical cancer: a systematic review

Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer. We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools. Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy. Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies. https://doi.org/10.17605/OSF.IO/WPHN5 [Figure: see text].

Comparison of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance therapy for newly-diagnosed and platinum-sensitive recurrent ovarian cancer with BRCA mutational status: a systematic review and network meta-analysis

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and overall safety of available PARPi as maintenance therapy for BRCA mutation status in patients with newly diagnosed and platinum-sensitive recurrent (PSR) OC patients. Relevant RCTs were systematically retrieved from PubMed and Embase until 31 May 2022. Progression-free survival (PFS) and overall survival (OS) based on In newly diagnosed BRCAm-OC patients, olaparib (HR: 0.33; 95% confidence interval [CI]: 0.25, 0.43) and other PARPis [niraparib (HR: 0.40; 95% CI: 0.29, 0.55), rucaparib (HR: 0.40; 95% CI: 0.21, 0.76) and veliparib (HR: 0.44; 95% CI: 0.28, 0.69)] had a statistically significant effect on PFS versus placebo. In BRCAm-PSROC patients, Olaparib exhibited significant benefit (HR: 0.69; 95% CI: 0.54, 0.88) for OS compared to other PARPis. In BRCAwt-PSR OC patients, Olaparib showed a favorable OS benefit than other PARPis (HR: 0.84; 95% CI: 0.57,1.22). Overall, safety profile of all PARPis was acceptable. All PARPis showed significant benefit, with olaparib showing greater benefit in newly diagnosed and PSR OC women. CRD42021288932.

Real-world experience with trabectedin for the treatment of recurrent ovarian cancer

An evaluation of selinexor as a maintenance therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma

Tumor protein 53 gene ( This review examines the mechanism of action of selinexor related to p53, contextualizes the effectiveness of selinexor among EC subtypes within the context of the evolving diagnostic, predictive, and therapeutic landscape for treatment, and presents the relevant clinical studies for selinexor dose for its use in gynecological malignancies. Literature review was conducted on the PubMed database. The promising efficacy signal suggests selinexor has potential as a maintenance therapy for

The current clinical approach to newly diagnosed uterine cancer

Uterine cancer is the most common gynecologic malignancy, although fortunately, 75% of women present with early-stage disease. A major area of controversy regarding the management of the disease concerns postoperative therapy for both women with early- and advanced-stage endometrial carcinoma. Here, we review landmark evidence that can help guide clinical decision-making in the treatment of women diagnosed with endometrial cancer. In this review, we present the latest data driving decisions for both surgical management and postoperative therapy for women with endometrial carcinoma. Areas discussed include surgical staging, with a specific discussion on the role of sentinel lymph node mapping, and postoperative therapy, ranging from the data supporting observation for women with early-stage, low-risk disease to combination therapy for women with advanced disease. Less common histologies, such as serous and clear cell carcinoma, as well as carcinosarcoma, will also be covered. Furthermore, a section of the paper is dedicated to the current state of fertility-sparing surgery. We suggest several approaches for deciding on adjuvant therapy, based on stage and histology, after comprehensive surgical staging. The role that endometrial cancer molecular subtypes will play on postoperative therapy remains to be fully investigated.

The role of HPV testing in the follow-up of patients in different clinical scenarios after diagnosis of cervical preinvasive lesions and carcinomas

Persistent human papillomavirus (HPV) infection is the causative factor for nearly all high-grade cervical lesions (CIN2/3) and invasive cervical cancers. HPV testing therefore plays a key role in the follow-up of patients treated surgically or managed conservatively. To optimize HPV testing in follow-up, we identified key clinical scenarios - conservative management of high-grade lesions, surveillance after conization or hysterectomy, post-surgical follow-up of cervical carcinoma, and monitoring after primary radiation therapy. We reviewed the evidence to propose a strategy for integrating HPV testing into follow-up. HPV testing shows high sensitivity and nearly 100% negative predictive value after conization for cervical high-grade lesions. Post-surgical HPV status is a more reliable predictor of recurrence than histopathological margin assessment. A negative result identifies patients with very low relapse risk. However, the lifetime risk of recurrent dysplasia remains increased and mainly depends on HPV status. Conversely, after fertility-sparing surgery for T1b cervical cancer, HPV testing alone is insufficient to rule out all recurrences. Its role is also unclear in patients after hysterectomy for invasive cancer and in those whose preinvasive lesions regressed spontaneously.

Development of a nomogram for predicting postoperative recurrence of cervical intraepithelial neoplasia using immunohistochemical and clinical parameters

We aimed to develop a nomogram to predict abnormal follow-up results of co-testing for cytology and human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) patients after conization. Two hundred sixty-three patients initially diagnosed as CIN2+ were recruited. Data on immunohistochemical (IHC) staining scores, along with demographic and clinical information were collected. Using least absolute shrinkage and selection operator (LASSO) regression analysis, variables were identified for inclusion. A predict model and nomogram were developed through multi-factor logistic regression. The goodness-of-fit test was applied across different cohorts to construct the calibration curve of the model, and the predictive effect was evaluated by the receiver operating characteristic curve. Decision curve analysis was performed to determine the net benefit. Five predictor variables, including protein expression score, vaginal infection, HPV coinfection, and cone height were screened and plotted as a nomogram. The calibration curves showed a good fit. The area under the curve of the model was 0.835 for the training cohort and 0.728 for the internal test cohort. The decision curve analysis indicated that the nomogram provides significant net advantages for clinical use. A practical nomogram predict model was developed to predict abnormal follow-up outcomes in CINs after conization.

Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer

Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FRα)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4. FRα is expressed in several epithelial cancers, including high grade serous ovarian cancer (HGSOC). Mirvetuximab received accelerated approval by the United States Food and Drug Administration (FDA) in November 2022 based on the results of the SORAYA trial, which tested mirvetuximab for the treatment of patients with recurrent platinum resistant HGSOC with high FRα expression and showed an overall response rate (ORR) of 32.4% and a median duration of response of 6.9 months. Mirvetuximab toxicities included low grade ocular and gastrointestinal toxicities. The National Comprehensive Cancer Network (NCCN) ovarian cancer 2023 guidelines adopted mirvetuximab as 2A, and mirvetuximab combined with bevacizumab as 2B, recommendations. This manuscript will review the preclinical and clinical development of mirvetuximab, the toxicities associated with mirvetuximab and mitigation strategies, and future applications of mirvetuximab. Mirvetuximab represents the first biomarker-directed therapy with an indication specifically for the treatment of PROC. The efficacy and favorable safety profile support further development of mirvetuximab and mirvetuximab combinations in platinum sensitive and newly diagnosed ovarian cancer.

Luteinized thecoma (thecomatosis) with sclerosing peritonitis: a systematic review of the literature of the last 25 years

Luteinized thecoma (thecomatosis) with sclerosing peritonitis (LTSP) is a very uncommon syndrome, characterized by the presence of single or bilateral ovarian thecomas and peritoneal fibrotic lesions. The disease occurs in young women and it can lead to peritoneal fibrosis and bowel obstruction. The pathogenesis of this syndrome remains still largely unknown. Surgery represents the cornerstone of treatment, but resection alone does not always allow a complete disease control. Attempts at medical treatments have been reported in recent years, but a real standard therapy has not yet been defined. We performed a systematic review of literature, collecting all the papers that reported cases of LTSP, since its first description in 1994. We found that, in these 25 years, less than 50 cases have been described in literature. Along with the established role of surgery, adjuvant treatment with hormonal agents, in particular in estrogen receptor expression, seems to be a promising approach. However, more efforts must be carried out to describe treatment and outcome of new cases, improving knowledge about this rare condition.

Luteinized thecomatosis and other conditions associated with sclerosing peritonitis: a problem in causation, management, and nomenclature

microRNAs as biomarkers of ovarian cancer

Targeted treatment options for the management of metastatic/persistent and recurrent cervical cancer

Cervical cancer is the overall fourth most common malignancy and the fourth most common cause of cancer-related deaths worldwide. Despite vaccination and screening programs, many women continue to present with advanced stage cervical cancer, wherein the treatment options have been limited. In this review, immunotherapy and the potential targeted therapies that have demonstrated promise in the treatment of persistent, recurrent, and metastatic cervical cancer are discussed. Our global goal in the gynecologic oncology community is to eliminate cervical cancer, by increasing the uptake of preventive vaccination and screening programs. For unfortunate patients who present with metastatic, persistent, and recurrent cervical cancer, pembrolizumab with chemotherapy, with or without bevacizumab is the new first-line therapy for PD-L1 positive patients. For this patient population as a second-line therapy, tisotumab vedotin (i.e. ADC) has shown significant efficacy in phase II trials, leading to the US Food and Drug Administration approval. Combination regimens inclusive of immune checkpoint inhibitors, DNA damage repair inhibitors, and antibody drug conjugates are potential breakthrough treatment strategies and are currently being investigated.

Treatment of cervical cancer: overcoming challenges in access to brachytherapy

Brachytherapy is an essential component of the cervical cancer treatment paradigm as it contributes to improved clinical outcomes and overall survival. Yet brachytherapy remains globally underutilized, with disparities in access at both national and international levels. The review explores current brachytherapy utilization practices and efforts being undertaken to address barriers to implementation in low-, middle-, and high-income countries, and how these efforts are projected to impact future brachytherapy access. The content presented is based on a review of published literature and the authors' collective clinical experiences. There exists a tremendous opportunity to expand access to essential brachytherapy services for women with cervical cancer. Many national and international brachytherapy efforts exist; yet it remains imperative that such focused efforts continue to grow and provide further access to this critical treatment modality for women in need worldwide.

Risk-reducing mastectomy in healthy women with BRCA mutation: a narrative review

Unveiling the power of PARP inhibitors: a meta-analysis on newly diagnosed advanced ovarian cancer maintenance therapy

This meta-analysis sought to assess the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as maintenance therapy for patients with newly diagnosed advanced ovarian cancer (OC). A comprehensive search was conducted across the PubMed, Medline, EMBASE, Cochrane Library, and Web of Science databases, up to 30 January 2025. Both pairwise meta-analysis and Bayesian network meta-analysis were employed. The primary end points were progression-free survival (PFS) and adverse events (AEs). A total of seven randomized controlled trials, encompassing 11 studies and 3220 patients, were included. PARPi maintenance therapy significantly improved PFS in patients with newly diagnosed OC. Subgroup analysis revealed PFS benefits across BRCA mutations, BRCA wild-type (BRCAwt), homologous recombination deficiency (HRD), and homologous recombination proficiency patients. However, no overall survival (OS) benefit was observed with PARPi maintenance therapy in either the overall or HRD populations. Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. Additionally, PARPi treatment was associated with a significantly higher incidence of grade ≥3 AEs. PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed. PROSPERO (CRD420251020275).

Relacorilant in recurrent ovarian cancer: clinical evidence and future perspectives

Relacorilant (CORT125134, Corcept Therapeutics) is a selective glucocorticoid receptor modulator, which reverses the glucocorticoid-mediated anti-apoptotic effects and restores the taxane chemosensitivity in epithelial ovarian cancer cells. Given those preclinical findings, relacorilant is currently under investigation in clinical trials in combination with nab-paclitaxel for the platinum-resistant ovarian cancer setting. Already published preclinical and clinical evidence of relacorilant antitumor activity was analyzed and discussed. Ongoing clinical trials registered on clincaltrials.gov were also reported. The review aimed to summarize the status of relacorilant, the mechanism of action, the published and ongoing trials, and its safety and efficacy. Relacorilant combined with nab-paclitaxel, may represent a promising strategy for the treatment of platinum-resistant ovarian cancer patients. After preliminary positive results in terms of clinical efficacy, a randomized phase III trial is ongoing to confirm the findings from the published phase II study.

Is there a link between talcum powder, oxidative stress, and ovarian cancer risk?

The link between talcum powder use and cancer, particularly ovarian cancer, has been a topic of scientific research and legal debate for several years. Studies have suggested a potential association between long-term talcum powder use in the genital area and an increased risk of ovarian cancer. The following report includes up-to-date evidence to support the potential link between talcum powder use and the risk of developing ovarian cancer. The International Agency for Research on Cancer, which is part of the World Health Organization, classified talc-based body powder as possibly carcinogenic to humans when used in the female genital area. However, other studies have not consistently supported this association, and thus more research is needed to establish a clear and definitive link between talcum powder use and cancer. Despite this, recent molecular-level data have linked talc to alterations in redox balance, gene mutations, and inflammatory responses. Specifically, we have identified a role for talc to induce the pro-oxidant state, inhibit apoptosis, and more importantly induced cellular transformation in normal ovarian cells. We presented unequivocal evidence to support our opinion that talc is not biologically inert and induces molecular changes that mimic the hallmarks of cancer.

Niraparib in the maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: safety and efficacy

Pembrolizumab for advanced cervical cancer: safety and efficacy

Is smoking an independent risk factor for developing cervical intra-epithelial neoplasia and cervical cancer? A systematic review and meta-analysis

Optimal treatment in locally advanced cervical cancer

Clinical differences among the PARP inhibitors in the first-line treatment of advanced-stage ovarian carcinoma

Despite favorable patient response rates to first-line chemotherapy, 5-year overall survival rates in ovarian cancer are dismal. Fortunately, the inclusion of PARP inhibitors (e.g. olaparib, niraparib, and rucaparib) following the completion of primary induction chemotherapy, has conferred improved progression-free survival rates. There are treatment outcome differences among the various PARP inhibitors that coincide with a patient's specific homologous recombination deficit (HRD) status; moreover, only single-agent olaparib and olaparib with bevacizumab have conferred a 5-year overall survival benefit. In the current review, we recount the clinical differences associated with the available PARP inhibitors in the management of advanced-stage ovarian carcinoma. The inclusion of PARP inhibitors has significantly improved survival benefits in advanced-stage ovarian cancer, especially among patients with an identifiable HRD. While there are tolerability differences inherent to the specific PARP inhibitors, not to mention approval distinctions, olaparib is the only PARP inhibitor that has demonstrated consistent overall survival benefits.

Statin use and ovarian cancer outcomes

Ovarian cancer contributed to 13,270 patient deaths in the United States during 2023 and is considered the most aggressive gynecologic malignancy. While surgery, chemotherapy and targeted medications have improved ovarian cancer patient outcomes, novel therapies that further bolster treatment efficacy without compromising toxicity represent an unmet clinical need. In the current review, we assessed the reported studies involving statin use and ovarian cancer outcomes; a preponderance of the evidence indicated that statins confer a survival benefit in ovarian cancer, especially for patients who underwent treatment post-diagnosis and for a prolonged interval. The evidence involving a potential survival benefit from statin use in ovarian cancer remains controversial, especially with hydrophilic statins (e.g. pravastatin). While statin users may exhibit better ovarian cancer survival outcomes than non-statin users, additional research should evaluate the putative clinical benefits of statins in ovarian cancer via randomized controlled trials.

Activation of ferritin light chain (FTL) by transcription factor salmonella pathogenicity island 1 modulates glycolysis to drive metastasis of ovarian cancer cells

Ovarian cancer (OC) is the most lethal gynecological cancer often diagnosed at an advanced stage due to a lack of effective biomarkers. Ferritin light chain (FTL) is implicated in the development of various cancers, but its impact on OC remains unknown. Bioinformatics methods were utilized to analyze FTL. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were employed for expression detection, and cell counting kit- 8, and transwell assays were for cell biological functions assessment. Extracellular acidification rate, oxygen consumption rate, and glycolytic metabolite contents were measured. Dual-luciferase and chromatin immunoprecipitation assay validated binding relationship. Xenografted tumor models in nude mice verified the role of FTL Cell function experiments revealed that FTL facilitated proliferation, migration, and invasion of OC cells. Rescue experiments unveiled that 2-Deoxy-D-glucose attenuated stimulation on OC cell metastasis and glycolysis by FTL overexpression. Salmonella pathogenicity island 1 (SPI1) up-regulated FTL expression to promote glycolysis and metastasis. FTL knockdown inhibited tumor growth and suppressed glycolysis and cell metastasis This study demonstrated pro-metastatic mechanisms of transcription factor SPI1/FTL axis in OC and suggested it as a potential target for treating OC metastasis.

Treatment options in the advanced and recurrent setting for endometrial cancer: an update

Uterine cancer is the most common gynecologic malignancy in women and is projected to surpass ovarian cancer as the deadliest gynecologic malignancy in the United States in 2024. Additionally, rates of advanced and high-risk uterine cancer have been on the rise in the United States, demonstrating a need for innovation in treatment options. There have been multiple recent trials investigating the incorporation of novel agents in the treatment of advanced and recurrent endometrial cancer. This article will discuss the current landscape of the treatment of advanced and recurrent endometrial cancer, focusing on recent phase III trials published or presented on with the incorporation of immunotherapy and other novel therapeutics while also reviewing promising phase I and II trials in the field. Clinical trials were identified via clinicaltrials.gov and a PubMed literature search was performed (initially February 2024, updated May 2024). The treatment field is promising for patients as many of these trials appear to offer progression free and overall survival benefits in a disease with a historically poor prognosis. Molecular profiling of endometrial cancer will be the backbone of treatment paradigms in the future.

Risks and benefits of sentinel lymph node evaluation in the management of endometrial intraepithelial neoplasia

Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer. Increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) evaluation during hysterectomy for EIN to ensure complete staging if there is cancer on the final specimen. However, there are no clear guidelines and the benefits and risks to performing SLN evaluation for EIN patients are unclear. This narrative review examines the advantages and disadvantages of SLN evaluation for EIN patients and provides an algorithm to assist clinicians in selectively applying the procedure for maximal patient benefit. Relevant articles up to March 2024 were obtained from a PubMed search on SLN use with endometrial pathology. Sentinel lymph node evaluation for patients with EIN is safe, feasible, and particularly important for the approximately 10% of patients with high-risk endometrial carcinoma on final pathology. However, as most diagnosed carcinomas are low-risk, SLN evaluation would have limited oncologic benefit. While SLN assessment may overtreat most patients with EIN, a significant minority of patients will be improperly staged. We propose an algorithm highlighting the importance of maximal preoperative endometrial sampling and stratifying patients via risk factors to selectively identify those who would benefit most from SLN evaluation.

Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer

The advent of immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the management of mismatch repair deficient (MMR-d)/microsatellite instability-high (MSI-H) endometrial cancer (EC). Initially investigated as monotherapy in phase I-II clinical trials for recurrent disease, immunotherapy demonstrated remarkable activity, yielding overall response rates (ORR) ranging from 27% to 58%. Based on these promising findings, phase III trials have explored the integration of immunotherapy into first-line treatment regimens for advanced/recurrent EC in combination with chemotherapy or other agents such as tyrosine kinase inhibitors (TKIs), resulting in improved ORR, progression-free survival, and overall survival compared to the standard chemotherapy regimen of paclitaxel and carboplatin. As a result, the incorporation of ICIs with standard platinum-based chemotherapy is becoming a new standard of care in MMR-d/MSI-H EC. This review synthesizes literature from PubMed, Embase databases, and recent congress abstracts on gynecological cancers. It covers MMR-d/MSI-H EC incidence, molecular diagnostics, clinical trial outcomes, predictive biomarkers for ICIs, patient profiles likely to benefit, resistance mechanisms, and the future of immunotherapy in this setting. By offering a comprehensive overview, this review delineates the pivotal role of ICIs in the management of MMR-d/MSI-H EC.

PD-1/PD-L1 inhibitors in endometrial cancer with high microsatellite instability: a Kaplan-Meier-derived patient data meta-analysis

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in women with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR). A systematic search was conducted in PubMed, Scopus, Cochrane, and Web of Science databases to compare PD-1/PD-L1 inhibitors versus standard therapy in patients with advanced/recurrent EC. Studies were screened based on predefined inclusion/exclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias Tool. We used DerSimonian and Laird random-effects models to estimate hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs). Five studies including 2,739 patients were analyzed, with 627 (22.90%) having dMMR tumors. ICIs significantly improved progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR patients. No significant difference was found in objective response rate (RR 1.72; 95% CI 0.88-3.36). The addition of immunotherapy for treating patients with advanced or recurrent endometrial cancer with dMMR and high microsatellite instability significantly improved PFS and OS outcomes. PROSPERO (CRD22057890200).

Toward clinical translation of AI-Led drug discovery in endometrial cancer

Deep learning (DL) is transforming cancer research by enabling data-driven drug discovery. However, its clinical translation, particularly in endometrial cancer (EC), faces significant challenges. This review discusses recent DL applications across drug discovery stages in EC, including target identification, virtual screening, and de novo drug design. We highlight key obstacles that hinder clinical translation, such as data scarcity, limited model explainability, biological validation gaps, and regulatory uncertainty, and propose practical solutions. Literature was sourced from PubMed, Web of Science, and relevant AI repositories, with an emphasis on peer-reviewed studies from the past five years. Despite early success, DL must overcome multiple translational bottlenecks to impact EC therapeutics meaningfully. A multidisciplinary approach that incorporates data quality improvements, functional validation, regulatory engagement, and clinician-focused decision support is essential to fully realize the clinical promise of DL-driven drug discovery in EC.

Innovations in laparoscopic management of endometrial cancer

Endometrial cancer is one of the most common gynecologic malignancies, with increasing incidence, in developed countries. Advances in minimally invasive surgery, particularly laparoscopic with or without the use of computer-assisted ('robotic') platforms, have transformed its management, improving surgical outcomes and patient recovery. This review explores recent innovations in laparoscopic management of endometrial cancer, including robotic-assisted laparoscopic surgery, sentinel lymph node mapping, and the integration of artificial intelligence in surgical navigation. A comprehensive literature search was conducted using PubMed and clinical trial databases to assess the impact of these advancements on surgical precision, oncologic outcomes, and patient recovery. Major studies comparing robotic-assisted laparoscopy, traditional laparoscopy, and open surgery are reviewed, along with new technologies that support real-time decision-making during surgery. Minimally invasive approaches have become the standard of care for early-stage endometrial cancer, offering superior perioperative outcomes. While robotic-assisted surgery provides technical advantages, cost and accessibility remain challenges. Sentinel lymph node mapping reduces morbidity compared to full lymphadenectomy, and artificial intelligence holds promise in optimizing surgical precision. Future research should focus on refining these technologies, improving patient selection criteria, and ensuring equitable access to advanced surgical techniques.

Pembrolizumab plus lenvatinib combination therapy for advanced endometrial carcinoma

Advanced and recurrent endometrial carcinoma remains a difficult diagnosis to treat due to the limited and ineffective available treatment options following platinum and taxane chemotherapy. Patients who are microsatellite stable (MSS) or mismatch repair proficient (pMMR) have even poorer outcomes with fewer effective therapies. Fortunately, recent Phase Ib/II and Phase III trials have demonstrated that combination pembrolizumab and lenvatinib resulted in improved ORR, PFS, and OS than currently used therapies in this setting. In this article, we review the history and notable clinical trials responsible for the advancement and status of treatment options available for advanced endometrial cancer. Most importantly, we review the recently published data on the efficacy, safety, and tolerability of the combination pembrolizumab and lenvatinib in advanced and recurrent endometrial cancer. The combination pembrolizumab and lenvatinib is an effective treatment regimen for patients with advanced and recurrent endometrial cancer who are MSS or pMMR who have failed prior platinum-based treatment. This combination should be routinely offered to patients following progression or recurrence of systemic platinum and taxane chemotherapy. Although this regimen is safe and effective, clinicians should be aware of the known toxicities and assess patients regularly to determine if dose modifications or interruptions are indicated.

The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research

Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients. This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored. There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.

Malignant peritoneal cytology in endometrial cancer: a contemporary review

In endometrial cancer, malignant peritoneal cytology (MPC) refers to the presence of tumor cells in the peritoneal cytologic specimen obtained at hysterectomy. MPC was once a component of uterine cancer staging criteria, but it is no longer included in the current revision. Multiple societies and organizations, however, continue to recommend peritoneal cytologic testing at the time of hysterectomy for endometrial cancer. This contemporary review provides a clinical summary of recent studies evaluating MPC, including risk factors and prognosis. Compared to prior studies showing a lack of impact on oncologic outcome, recent studies have larger sample sizes, use stricter inclusion criteria, and perform histology/cancer stage-specific analyses to balance risk factors and provide explicit interpretations for oncologic outcomes related to MPC. These newer data provide evidence that MPC does have a prognostic impact. Three key domains related to MPC are followings: First, recognition of MPC as a prognostic factor for endometrial cancer irrespective to stage (early and advanced) and histology (endometrioid and non-endometrioid) is necessary. Second, peritoneal cytologic testing at the beginning of each staging surgery is recommended. Last, incorporation of peritoneal cytology status in adjuvant treatment algorithms is useful and merits further development.

Immune checkpoint inhibitors for recurrent endometrial cancer

Endometrial cancer (EC) is the most common gynecologic malignancy. Outcomes for patients with advanced and/or recurrent disease have been modest with the use of chemotherapy. The approval of immune checkpoint inhibitors targeting PD-1 has recently revolutionized human cancer treatment. Recent trials with immune checkpoint inhibitors used alone or in combination with other agents, have demonstrated remarkable efficacy in the treatment of the all-comers EC patient population. In this article, we review major clinical trials on PD-1/PD-L1 inhibitors in advanced and recurrent EC and discuss the response rates of these agents in the context of their genomic background. Immune checkpoint inhibitors have significantly changed our approach to the treatment of advanced/recurrent EC. Single agent anti-PD-1 regimens are highly effective in MMRd/MSI-H patients, but their clinical efficacy remains modest in MMR proficient/TMB low EC patients. Combination regimens that can decrease the tumor microenvironments immunosuppression and increase tumor immunogenicity represent a viable treatment option to broaden the activity of immune checkpoint inhibitors in advanced/recurrent EC patients. An increased understanding of the biomarkers of response and the molecular mechanisms of resistance to immune checkpoint inhibitors remains key for the next advancement of the field.

The interplay between angiogenesis and cervical cancer: a comprehensive review

Cervical cancer is still a major global health threat, specifically in countries with little access to health services. Angiogenesis in cervical cancer not only contributes to tumor growth, metastasis, and resistance to therapy but also serves as a therapeutic target itself. This gives hope for the possible therapy. This review covers key molecular mechanisms in cervical cancer, including VEGF/VEGFR, HIF-1α, and PI3K/Akt pathways. It also discusses anti-angiogenic therapies like bevacizumab, small-molecule compounds, and emerging approaches such as nanoparticle-based drug delivery. Emphasis is placed on angiogenesis-related biomarkers for diagnosis and treatment selection, stressing the need for affordable therapies in low-resource settings. A literature search was conducted using PubMed, Scopus, and Google Scholar up to March 2025, focusing on VEGF/VEGFR signaling, anti-angiogenic therapies, and resistance mechanisms in cervical cancer. Despite promise, resistance, toxicity, and cost remain major challenges for anti-angiogenic therapy's clinical use. Combination strategies with immunotherapy, chemotherapy, and targeted agents may be more effective. Precision medicine using multi-omics and AI offers hope for better outcomes. Future studies should evaluate drug combinations with synergistic effects and develop management strategies to universalize innovative treatments.

Evaluating the efficacy and safety of trebananib in treating ovarian cancer and non-ovarian cancer patients: a meta-analysis and systematic review

Due to its anti-angiogenic properties, trebananib is frequently employed in the treatment of cancer patients, particularly those with ovarian cancer. We conducted a meta-analysis to assess the efficacy and safety profile of trebananib in combination with other drugs for treating both ovarian and non-ovarian cancer patients. Our search encompassed PubMed, Medline, Cochrane, and Embase databases, with a focus on evaluating study quality. Data extraction was conducted from randomized controlled trials (RCTs), and RevMan 5.3 facilitated result analysis. Combining trebananib with other drugs extended progression-free survival (PFS) [HR 0.81, (95%CI: 0.65, 0.99), Trebananib plus other drugs can improve the PFS, OS and ORR in patients with cancer, especially ovarian cancer. Our recommendation is to use trebananib plus other drugs to treat advanced cancer, and to continuously monitor and manage drug-related adverse events. PROSPERO (No. CRD42023466988).

Safety and efficacy of Rucaparib in the treatment of ovarian cancer and patients with BRCA mutation: a systematic review and meta-analysis of phase III randomized clinical trials

Our systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of Rucaparib, a PARP inhibitor (PARPi), in patients with ovarian cancer and BRCA mutation. Online databases were comprehensively searched for all phase III Randomized trials that used Rucaparib therapy for ovarian cancer patients and patients having BRCA mutation. Efficacy results are progression-free survival and overall response rate in addition to addressing its safety concerns. After pooling data from 4 clinical trials, the analysis showed a significant improvement in PFS among ovarian cancer patients and for the maintenance therapy with a hazard ratio (HR) of 0.49 (95% CI 0.34-0.73, Rucaparib demonstrated significant efficacy in improving PFS and ORR in ovarian cancer patients, particularly those having BRCA mutations. However, they should be closely monitored due to the greater risk of various adverse effects.

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma

Endometrial cancer can be characterized by high instability of microsatellites (MSI-H), a biomarker indicative of sensibility to immune checkpoint inhibitors (ICIs). The results of the KEYNOTE-158 trial led to the approval of pembrolizumab - a monoclonal, humanized IgG4 kappa anti-PD-1 antibody able to prevent T-cell PD-1/tumor cell PD-L1/2 interaction, thus restoring T-cell-mediated anti-tumor immunity - in MSI-H endometrial cancer relapsing after at least one line of chemotherapy (CT). Ongoing trials, such as KEYNOTE-B21/ENGOT-en11, KEYNOTE-C93/ENGOT-en15/GOG-3064, and NRG/GY018, aim to move this option earlier in the algorithm, whether adjuvant or first-line, even CT-free. Combinatorial approaches associating ICIs with other target therapies blocking immunosuppressive pathways are also being studied. The ICI overall response rates in MSI-H patients are encouraging, but over 50% do not respond to treatment. A more thorough definition of the MSI status regarding specific missing proteins could allow better use of this biomarker and explain why specific populations may not respond to immunotherapy regardless of widely accepted predictive biomarkers. Future developments should focus on identifying who can benefit from a CT-free treatment and translational research on primary resistant MSI-H EC.