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Background: Isolated mediastinal metastases from ovarian carcinoma are considered exceptional. Since such metastases are considered advanced stage disease, systemic therapy is the indicated therapeutic approach; however, some articles report that surgical excision is also feasible. Methods: We reviewed the English-language literature to detect cases of isolated mediastinal ovarian cancer metastases and present the management applied as well as their outcomes. Results: From 1998 to 2022, 15 such cases have been reported, with 4 of those cases being primary ovarian cancer presentation and 11 being ovarian cancer recurrence. The histology of the tumor was serious in all of the cases. Regarding the management of cancer, various methods were applied. In total, 11 of the patients underwent a surgical resection of the mediastinal metastasis, 2 received systemic therapy, 1 received a combination of palliative chemotherapy and radiation and the last patient was treated with laser debulking and radiotherapy. The mean reported follow-up was 11 months. Conclusions: Solitary mediastinal metastasis from ovarian cancer is very rare; physicians should pay close attention when routinely evaluating thoracic scans from patients with ovarian malignancy as well as individualizing the management in such patients, since surgical resection can also be performed. However, definitive conclusions cannot be drawn from the small number of case reports available. [ABSTRACT FROM AUTHOR]

Simple Summary: For a couple of decades, the morbidity rates for endometrial cancer (EC) have been on a constant rise. Surgery is the cornerstone in the management of this disease and may be performed for curative, staging, or palliative purposes. The type of hysterectomy, the role and extent of lymphadenectomy, the procedure of the sentinel lymph node mapping, and cytoreductive surgery in advanced or recurrent EC are discussed in detail. Most recently, the introduction of the molecular classification has changed the scene in EC treatment, and its impact on choosing the surgical strategy is outlined. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject providing an up-to-date clinical guide. Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade serous ovarian cancer is a rare type of ovarian cancer that usually has an indolent growth and affects younger women. It has markers that suggest it might respond to hormone therapy, but unfortunately, this treatment does not work well for many patients because the cancer becomes resistant to it. We do not fully understand why this happens. In breast cancer, similar resistance mechanisms are studied, so we are exploring if we can apply what we learn there to improve treatment for this type of ovarian cancer. This review looks at why hormone therapy might stop working in ovarian cancer and explores new ways to make it more effective. The goal is to find better treatment options for patients with advanced low-grade serous ovarian cancer, who currently do not have many choices for treatment. Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is one of the most aggressive forms of gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as most patients are diagnosed with advanced disease. Debulking surgery and platinum-based therapies are the current mainstay for OC treatment. However, and despite achieving initial remission, a significant portion of patients will relapse because of innate and acquired resistance, at which point the disease is considered incurable. In view of this, novel detection strategies and therapeutic approaches are needed to improve outcomes and survival of OC patients. In this review, we summarize our current knowledge of the genetic landscape and molecular pathways underpinning OC and its many subtypes. By examining therapeutic strategies explored in preclinical and clinical settings, we highlight the importance of decoding how single and convergent genetic alterations co-exist and drive OC progression and resistance to current treatments. We also propose that core signalling pathways such as the PI3K and MAPK pathways play critical roles in the origin of diverse OC subtypes and can become new targets in combination with known DNA damage repair pathways for the development of tailored and more effective anti-cancer treatments. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cognitive impairment or "chemobrain" is a prevalent long-term complication of chemotherapy and one of the more devastating. Most of the studies performed so far to identify the cognitive dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered to breast cancer patients, a population that, after treatment, shows a high possibility of long survival and, consequently, of chemobrain development. In the last few years, different possible strategies have been explored to prevent or reduce chemobrain induced by the anthracycline doxorubicin (DOX), known to promote oxidative stress and inflammation, which have been strongly implicated in the development of this brain dysfunction. Here, we have critically analyzed the results of the preclinical studies from the last few years that have evaluated the potential of phenolic compounds (PheCs), a large class of natural products able to exert powerful antioxidant and anti-inflammatory activities, in inhibiting DOX-induced chemobrain. Several PheCs belonging to different classes have been shown to be able to revert DOX-induced brain morphological damages and deficits associated with learning, memory, and exploratory behavior. We have analyzed the biological and molecular mechanisms implicated and suggested possible future perspectives in this research area. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OC) is the most lethal gynecologic malignancy, with a relative 5-year survival rate of between 40% and 50%. We used the Cancer Registry of Baden-Württemberg to identify characteristics, treatment patterns and survival of OC patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV who were registered over a period of 8 years (2012–2019). The aim of the present analysis was to describe an unselected patient population with primary diagnoses of FIGO stage IV OC with respect to baseline patient and tumor characteristics, treatment strategies and prognosis in terms of overall survival. In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment. Background: The aim of the present study was to describe an unselected population of patients with diagnosis of FIGO stage IV OC. Methods: Data from 1183 patients were available for analysis. Results: The majority of patients (962/1183, 81.3%) received cancer-directed treatment. The median follow-up time was 3.8 years, and the median overall survival duration was 1.9 years. Notably, patients >80 years had a low overall survival rate (HR of age >80 years vs. ≤50 years was 3.81, 95%-CI [2.76, 5.27], p < 0.0001). The survival rate was best in patients with HGSOC (p < 0.0001). The highest overall survival rate was observed in patients in the group with surgical intervention followed by systemic treatment, with an unadjusted HR of 0.72, 95%-CI [0.59, 0.86], p = 0.007 vs. systemic treatment only. After adjustment for age and histology, survival differences between treatment schemes were smaller (HR 0.81, 95%-CI [0.66, 1.00], p = 0.12). Conclusions: In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This review significantly contributes to the research community by providing insights into the role of serum-based biomarkers for the diagnosis of ovarian cancer. It also provides a comprehensive overview of recent advancements in immunoassay detection and employing multiplex technology and SPR biosensors to identify CA125 and HE4 biomarkers. Furthermore, it addresses the challenges associated with these diagnostic methods. This valuable information not only enhances our understanding of ovarian cancer diagnosis but also serves as a reference point for researchers and clinicians working in the field, facilitating further advancements and improvements in early detection methods. Epithelial Ovarian Cancer (EOC) is a leading cause of cancer-related deaths among women, mainly due to a lack of early detection and screening methods. Advanced immunoassay techniques, such as Luminex and proximity extension assay (PEA) technology, show promise in improving EOC detection by utilizing highly sensitive and specific multiplex panels to detect multiple combinations of biomarkers. However, these advanced immunoassay techniques have certain limitations, especially in validating the performance characteristics such as specificity, sensitivity, limit of detection (LOD), and dynamic range for each EOC biomarker within the panel. Implementing multiplexing in point-of-care (POC) biosensors can enhance EOC biomarker detection, with Surface Plasmon Resonance (SPR) being a versatile option among optical biosensors. There is no study on multiplex SPR biosensors specifically tailored for diagnosing EOC. Recent studies have shown promising results in the single detection of EOC biomarkers using SPR, with LOD for cancer antigen 125 (CA125) at 0.01 U/mL−1 and human epididymis protein 4 (HE4) at 1pM. This study proposes a potential roadmap for scientists and engineers in academia and industry to develop a cost effective yet highly efficient SPR biosensor platform for detecting EOC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compared the long-term surgical outcomes of single-port laparoscopy with other surgical methods (multi-port laparoscopy, robot-assisted laparoscopy, and laparotomy) in endometrial cancer (EC) surgical staging. After conducting propensity score matching, all surgical methods demonstrated comparable survival outcomes with respect to disease-free survival and overall survival. Consequently, single-port laparoscopy is deemed a viable option for surgical staging in EC. This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared to multi-port (p = 0.001) and robot-assisted (p = 0.031) laparoscopy. Single-port laparoscopy resulted in a significantly higher 3-year OS than laparotomy (p = 0.013). After propensity score matching, the four groups demonstrated similar survival outcomes (3-year DFS: p = 0.533; 3-year OS: p = 0.328) and recurrence rates (10.3%, 12.1%, 10.3%, and 15.9% in the single-port, multi-port, and robot-assisted laparoscopy and laparotomy groups, respectively, p = 0.552). Recurrence most commonly occurred in distant organs. The single-port laparoscopy group had the longest operative time (205.1 ± 76.9 min) but the least blood loss (69.5 ± 90.8 mL) and the shortest postoperative hospital stay (5.2 ± 2.3 days). In contrast, the laparotomy group had the shortest operative time (163.4 ± 51.0 min) but the highest blood loss (368.3 ± 326.4 mL) and the longest postoperative hospital stay (10.3 ± 4.6 days). The transfusion rate was 0% in the single-port laparoscopy group and 3.7% in the laparotomy group. Notably, the laparotomy group had the highest wound complication rate (p = 0.001), whereas no wound hernias were observed in the three minimally invasive approaches. In conclusion, the survival outcomes were comparable between the methods, with the benefit of lower blood loss and shorter hospital stay observed in the single-port laparoscopy group. This study suggests that single-port laparoscopy is a feasible approach for endometrial cancer surgical staging. [ABSTRACT FROM AUTHOR]

Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future. [ABSTRACT FROM AUTHOR]

Background: Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. Objective: The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. Methods: A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. Results: Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. Conclusions: TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is often diagnosed only in advanced stages, which limits therapeutic options and prognosis. Therefore, better and easily accessible methods for the early diagnosis of ovarian cancer are needed. In particular, blood-based biomarkers seem to be promising candidates for the accurate detection of ovarian cancer. We determined the concentrations of the two proteins HMGB1 and sRAGE in the sera of 231 women with ovarian cancer, benign diseases and without known gynecologic disease. In the analyses of receiver operating characteristics, both HMGB1 and sRAGE could distinguish patients with ovarian cancer from healthy women (area under the curve (AUC) 0.77 and 0.65), benign diseases (AUC 0.72 and 0.61) or all non-malignant cases (AUC 0.74 and 0.63). Moreover, the ratio of HMGB1/sRAGE differentiated even better between malignancies and other cases (AUC 0.78, 0.74 and 0.76, respectively). In conclusion, HMGB1 and sRAGE are potential candidates for the development of assays for early diagnosis of ovarian cancer and warrant inclusion in further validation studies. Background: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may serve as novel diagnostic tools for cancer diagnosis. Methods: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. Results: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. Conclusion: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex (MHC) loci, the most polymorphic regions within the human genome, encode protein complexes responsible for antigen presentation and CD4+ and CD8+ cell activation. In prostate cancer (PCa), the second most diagnosed cancer in the male population, MHC loci undergo significant changes in their expression patterns, which affect the ability of the immune system to attack and eliminate malignant cells. The purpose of this study was to explore the genetic diversity of human leukocyte antigen (HLA)-A and HLA-B in patients with PCa and healthy controls (HCs) by performing HLA genotyping using NGS technology. The analysis highlighted statistically significant differences (p < 0.05) in the prevalence of three alleles (A*11:01, A*24:02, and B*18:01). Among the HCs analyzed, 14.89% had A*11:01, 20.21% had A*24:02, and 30.61% had B*18:01; while 5.21% of patients with PCa presented A*11:01, 9.38% presented A*24:02, 18.08% presented B*18:01. Odds ratio (OR) calculations underlined a negative association between the three alleles and the risk of PCa (OR < 1). The results presented in this study suggest a protective role of A*11:01, A*24:02, and B*18:01 in PCa. [ABSTRACT FROM AUTHOR]

Recently, we have shown that HLA-A*02:01 and HLA-A*24:02 in de novo metastatic prostate cancer (MPCa) have an important role in disease progression. Since de novo MPCa represents a small group among patients diagnosed with prostate cancer (PCa), it was obvious to try to extend the validity of our results to larger cohorts of PCa patients. Herein, we analyzed patients irrespective of their disease status at diagnosis to include, besides patients with MPCa, those with localized PCa (LPCa). Our goal was to specify the prognostic value of HLA-A*02:01 and HLA-A*24:02 for overall survival (OS) prospectively and for early biochemical recurrence (BCR) and castrate resistance (CR) as additional clinical endpoints in a prospective/retrospective manner, to improve clinical decisions for patients covering all stages of PCa. On univariate analysis, HLA-A alleles were significantly associated as prognostic biomarkers with early BCR (p = 0.028; HR = 1.822), OS (p = 0.013; HR = 1.547) and showed a trend for CR (p = 0.150; HR = 1.239). On multivariate analysis, HLA-A alleles proved to be independent prognosticators for early BCR (p = 0.017; HR = 2.008), CR (p = 0.005; HR = 1.615), and OS (p = 0.002; HR = 2.063). Kaplan–Meier analyses revealed that patients belonging to the HLA-A*02:01+HLA-A*24:02− group progressed much faster to BCR and CR and had also shorter OS compared to HLA-A*24:02+ patients. Patients being HLA-A*02:01−HLA-A*24:02− exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment. [ABSTRACT FROM AUTHOR]

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The identification of prognostic factors is important to improve the management of patients with ovarian cancer (OC). The staging classification of OC was revised in 2014 and 2018 by the FIGO (International Federation of Gynecology and Obstetrics) Gynecological Oncology Committee and dichotomizes stages IV into stage IVA and IVB. The FIGO classification aims to establish a disease severity scale and to group patients with similar prognoses. The objective of our retrospective, multicenter study was to assess the prognostic impact of this dichotomization and of the initial metastatic localization of patients with FIGO stage IV OC. We showed that, among our 307 patients, FIGO stage IVA patients had a worse prognosis than FIGO stage IVB patients. The initial pleural effusion was a factor of poor prognosis in terms of overall survival. We suggest a modification of the current FIGO staging classification. International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the identification of a large variety of biomarkers in B cell malignancies as being driving factors for tumor progression and patient prognosis, their targeting may confer valuable options for the treatment of these diseases. Over the past 20 years, the permanent development of a multitude of inhibitors acting on survival-associated biomarkers has made it into clinical evaluation in B lymphoid tumors. Although certain drugs approved by the US Food and Drug Administration improve clinical outcome, some patients do not respond and others relapse. This review summarizes the current state-of-the-art, provides a summary of new, safer, more selective inhibitors currently under evaluation in clinical trials, and highlights the emerging positioning of metabolic drugs in tumor B cell biology as a promising strategy to be translated into clinical practice. Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today's commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton's tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. We evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We found that, to prevent misidentification, it is necessary to understand the underlying disease that can increase tumor marker levels or benign tumors, which are difficult to distinguish from malignant tumors in imaging tests and several rare histopathologies with low risk of ovarian malignancy algorithm values. The malignant prediction of tumor markers and imaging was different in many patients with ovarian tumors, and this study will help to reduce the misidentification of tumors. Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. Therefore, we evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We enrolled 1047 patients with ovarian tumors. The predictive values and concordance rates between the preoperative risk of ovarian malignancy algorithm (ROMA) and imaging, including CT and MRI, were evaluated. Diagnoses of 561 CT (77.9%) and 322 MRI group (69.2%) participants were consistent with the ROMA. Among them, 96.4% of the CT (541/561) and 92.5% of the MRI (298/322) group predicted an accurate diagnosis. In contrast, 67.3% (101/150) of CT and 75.2% (100/133) of MRI cases accurately predicted the diagnosis in cases with discrepancies between ROMA and CT or MRI; a total of 32% (48/150) of the CT and 25.5% (34/133) of the MRI group showed an accurate ROMA diagnosis in cases with discrepancies between ROMA and imaging. In the event of a discrepancy between ROMA and imaging when ovarian tumor malignancy prediction, the question is which method should take precedence. This study demonstrates that MRI has the greatest diagnostic accuracy, followed by CT and ROMA. It is also important to understand underlying diseases and benign conditions and rare histopathologies of malignant tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Standard treatment of advanced stage epithelial ovarian cancer consists of cytoreductive surgery (CRS) and chemotherapy. Prolonged progression free and overall survival is correlated with the amount of residual tumor after CRS. However, cytoreductive surgery is an extensive procedure with a considerable risk of postoperative complications. Therefore, it would be valuable to have parameters that can predict the surgical outcome. In this study, we evaluated the value of the blood tumor marker CA-125 to predict complete CRS to no residual tumor. The results of our study suggest that CA-125 levels ≤35 kU/L significantly predict the surgical outcome in patients who underwent interval cytoreductive surgery, but this parameter cannot be used as an independent predictor. This contrasts with the outcome of our systematic review with mainly retrospective data, which found CA-125 as an independent predictive variable. Background: The tumor marker 'cancer antigen 125' (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. Methods: A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial named "PlaComOv-study". A regression analysis was performed to demonstrate correlations between preoperative CA-125 levels, CA-125 reduction after NACT, and surgical outcome. Results: Fourteen relevant articles were analyzed of which eleven reported that lower preoperative CA-125 levels were associated with a higher probability of complete cytoreduction. In the clinical study, 326 patients with FIGO stage IIIB-IV ovarian cancer who underwent CRS were enrolled from 2018 to 2020. Patients who underwent interval CRS with preoperative CA-125 levels ≤35 kU/L had higher odds of achieving complete CRS than patients with CA-125 level >35 kU/L (85% vs. 67%, OR 2.79, 95%CI 1.44–5.41, p = 0.002). In multivariable analysis with presence of ascites and peritoneal carcinomatosis, normalized preoperative CA-125 did not appear as a significant predictor for complete CRS. Conclusions: In literature, preoperative CA-125 levels ≤35 kU/L were associated with a significant higher percentage of complete CRS in univariable analysis. According to our cohort study, preoperative CA-125 level ≤35 kU/L cannot independently predict surgical outcome either for primary or interval CRS. [ABSTRACT FROM AUTHOR]

Simple Summary: The issue of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGS-EOC) has hampered the possibility to shape the molecular portrait of relapsed disease, which ultimately impacts our ability to develop a more rational second-line treatment. Liquid biopsy offers the unique opportunity to track tumor evolution over time and infer the dynamic changes of tumor clonal architecture. Differently from other tumors, no actionable driving lesions characterize HGS-EOC, thus genome-scale analysis like whole-exome sequencing is not compatible with the clinical turnaround time. In the present work, we provided a novel framework based on the analysis of both qualitative and quantitative features of circulating tumor DNA (ctDNA) in order to identify, at the time of molecular relapse, the early genetic vulnerabilities that will characterize the clinical recurrence and thus be amenable of a more rational second-line treatment. We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through plasma sample analysis a real-time picture of those emerging molecular lesions that will drive and sustain the growth of relapsed disease and ultimately will confer resistance. In this proof of principle study, the same genomic libraries obtained at the diagnosis (T0), TRm and TRc were further analyzed by targeted resequencing approach to sequence the coding region of a panel of 65 genes to provide longitudinal analysis of clonal evolution as a novel strategy to support clinical decisions for the second-line treatment. Experiments were performed on plasma and tumor tissues withdrawn on a selection of previously analyzed cohorts of cases (i.e., 33 matched primary and synchronous lesions and 43 plasma samples from 18 patients). At T0, the median concordance of mutations shared by each tumor tissue biopsy and its matched plasma sample was 2.27%. This finding confirms the limit of a single tumor biopsy to be representative of the entire disease, while plasma analysis can recapitulate most of the main molecular lesions of the disease. A comparable scenario was observed during longitudinal analysis, where, with the exception of the TP53 gene and germline mutations in BRCA1/2 genes, no other gene shared the same locus specific gene mutation across T0, TRm and TRc time points. This high level of temporal heterogeneity has important implications for planning second-line treatment. For example, in three out of 13 cases, plasma ctDNA analysis at TRm or TRc reported acquired novel variants in the TP53BP1 gene not present at T0. In particular, patient 21564, potentially eligible for PARP-inhibitor (PARPi) treatment at the time of diagnosis (BRCA1 c.5182delA mutation), would unlikely respond to these drugs in second-line therapy due to the presence of eight distinct TP53BP1 variants in plasma samples collected TRc. This study demonstrates that liquid biopsy provides a real-time molecular picture to intercept those actionable genetic vulnerabilities or drug resistance mechanisms that could be used to plan a more rational second-line treatment. [ABSTRACT FROM AUTHOR]

Most ovarian cancer cases are diagnosed at an advanced stage (III or IV), in which a primary debulking surgery combined with adjuvant systemic chemotherapy is the standard management. Since targeted therapy is less toxic to human cells than systemic chemotherapy, it has drawn much attention and become more popular. Angiogenesis is a critical process during the proliferation of ovarian cancer cells. Currently, many studies have put emphases on anti-angiogenetic medication, such as bevacizumab, the first and most investigated angiogenesis inhibitor that can exert anti-neoplastic effects. Bevacizumab is a recombinant humanized monoclonal antibody that has been approved for first-line maintenance treatment of advanced ovarian cancer. This review is a summary of current literature about the molecular mechanisms of actions, safety, and effects of bevacizumab for use in advanced epithelial ovarian cancer. Some common side effects of bevacizumab will be also discussed. As an inhibitor of angiogenesis, bevacizumab binds to circulating vascular endothelial growth factor (VEGF) and thereby inhibits the binding of VEGF to its receptors on the surface of endothelial cells. Neutralization of VEGF prevents neovascularization and leads to apoptosis of tumor endothelial cells and a decrease in interstitial fluid pressure within the tumors, which allows greater capacity for chemotherapeutic drugs to reach specific targeted sites. Grossly, bevacizumab has demonstrated some significant therapeutic benefits in many randomized trials in combination with the standard chemotherapy for advanced epithelial ovarian cancer. Based on the available evidence, a higher dosage and a longer duration of bevacizumab appear to achieve better therapeutic effects and progression-free survival. On the other hand, patients with more severe diseases or at a higher risk of progression seem to benefit more from bevacizumab use. However, many unknown aspects of bevacizumab, including detailed mechanisms of actions, effectiveness, and safety for the treatment of ovarian cancer, warrant further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Fatigue in older patients has multiple etiologies, as this symptom may be cancer-related, treatment-related, age-related, or part of frailty syndrome. Physicians need to identify this symptom and understand its risk factors but also evaluate the risk/benefit ratio of cancer treatments considering the risk of impairing the patient's quality of life. This scoping review was aimed to present the level of information currently available on any-grade fatigue and grade 3 or more fatigue for each cancer treatment regimen, either in general or in older populations, for the most prevalent tumors. Fatigue is a highly prevalent symptom in both cancer patients and the older population, and it contributes to quality-of-life impairment. Cancer treatment-related fatigue should thus be included in the risk/benefit assessment when introducing any treatment, but tools are lacking to a priori estimate such risk. This scoping review was designed to report the current evidence regarding the frequency of fatigue for the different treatment regimens proposed for the main cancer indications, with a specific focus on age-specific data, for the following tumors: breast, ovary, prostate, urothelium, colon, lung and lymphoma. Fatigue was most frequently reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versions 3 to 5. A total of 324 regimens were analyzed; data on fatigue were available for 217 (67%) of them, and data specific to older patients were available for 35 (11%) of them; recent pivotal trials have generally reported more fatigue grades than older studies, illustrating increasing concern over time. This scoping review presents an easy-to-understand summary that is expected to provide helpful information for shared decisions with patients regarding the anticipation and prevention of fatigue during each cancer treatment. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the fifth leading cause of cancer deaths in women and is regarded as one of the most difficult cancers to treat. Currently, studies are being conducted to develop therapeutic agents for effective treatment of ovarian cancer. In this review, we explain the properties of the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) and how the signaling pathway of HGF/c-MET is activated in different cancers and involved in tumorigenesis and metastasis of ovarian cancer. We present the findings of clinical studies using small chemicals or antibodies targeting HGF/c-MET signaling in various cancer types, particularly in ovarian cancer. We also discuss that HGF/c-MET-targeted therapy, when combined with chemo drugs, could be an effective strategy for ovarian cancer therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30–50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4–7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30–50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Diabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. To the best of our knowledge, this review conducted the largest and most up-to-date meta-analysis to compare the incidence of diabetes between cancer patients and the cancer-free population. Our results suggest that new-onset diabetes is positively associated with cancer. Background: Diabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. Methods: A systematic electronic literature search was carried out from cohort studies regarding the incidence of diabetes in cancer patients, using the databases PubMed (MEDLINE), Embase, Web of Science, and the Cochrane Library. Random-effects meta-analyses were conducted to pool the estimates. Results: A total of 34 articles involving 360,971 cancer patients and 1,819,451 cancer-free controls were included in the meta-analysis. An increased pooled relative risk (RR) of 1.42 (95% confidence interval (CI): 1.30–1.54, I2 = 95, τ2 = 0.0551, p < 0.01) for diabetes in cancer patients was found compared with the cancer-free population. The highest relative risk was observed in the first year after cancer diagnosis (RR = 2.06; 95% CI 1.63–2.60). Conclusions: New-onset diabetes is positively associated with cancer, but this association varies according to cancer type. More prospective studies with large sample sizes and longer follow-up times are advocated to further examine the association and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

The term liquid biopsy reveals a non-invasive diagnostic method that might be based on the quantification of cell-free microRNAs in body fluids. However, the identification of candidates for liquid biopsy is challenging. Our aim was to compare the cell-free expression of miR-483-5p, miR-205-5p, and let-7f-5p in ovarian cell cultures and plasma samples of patients with ovarian cancer. Both the intracellular and cell-free expression of miR-205-5p and let-7f-5p proved to be higher in the Estrogen Receptor α (ERα) expressing PEO1 cell-line than in the estrogen non-sensitive A2780. Moreover, the expression of let-7f-5p was up-regulated in response to estradiol exposure that was diminished after the addition of an ERα selective antagonist. MiR-483-5p had lower intracellular and cell-free expression in PEO1. All these miRNAs had detectable expression level in plasma samples, among which miR-205-5p proved to be overexpressed in the plasma samples of patients with ovarian tumors compared to healthy controls and possessed an acceptable diagnostic potential with ROC-AUC 0.683 (95% CI 0.57–0.795). Functional annotation clustering of the target genes of miR-205-5p revealed several clusters involved in cancer development. We suggest that miR-205-5p might be a promising biomarker candidate in ovarian cancer that should be further analyzed in larger sample size. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies. The late diagnosis is frequent due to the absence of specific symptomatology and the molecular complexity of the disease, which includes a high angiogenesis potential. The first-line treatment is based on optimal debulking surgery following chemotherapy with platinum/gemcitabine and taxane compounds. During the last years, anti-angiogenic therapy and poly adenosine diphosphate-ribose polymerases (PARP)-inhibitors were introduced in therapeutic schemes. Several studies have shown that these drugs increase the progression-free survival and overall survival of patients with ovarian cancer, but the identification of patients who have the greatest benefits is still under investigation. In the present review, we discuss about the molecular characteristics of the disease, the recent evidence of approved treatments and the new possible complementary approaches, focusing on drug repurposing, non-coding RNAs, and nanomedicine as a new method for drug delivery. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer has the highest lethality among gynecological tumors. Therefore, it is essential to find reliable biomarkers to improve early detection. This is the first report describing ADAM17 detection in serum and ascites fluid of ovarian cancer patients. A high ADAM17 concentration in serum at primary diagnosis is associated with early FIGO stages and predicts complete resection of the tumor mass. In addition, ADAM17 and CA-125 complement each other, especially in the diagnosis of early stages. In summary, ADAM17 appears to be a promising screening marker for detecting early-stage ovarian cancer. Ovarian cancer has the highest mortality rate among gynecological tumors. This is based on late diagnosis and the lack of early symptoms. To improve early detection, it is essential to find reliable biomarkers. The metalloprotease ADAM17 could be a potential marker, as it is highly expressed in many solid tumors, including ovarian and breast cancer. The aim of this work is to evaluate the relevance of ADAM17 as a potential diagnostic blood-based biomarker in ovarian cancer. Ovarian cancer cell lines IGROV-1 and A2780, as well as primary patient-derived tumor cells obtained from tumor tissue and ascitic fluid, were cultured to analyze ADAM17 abundance in the culture supernatant. In a translational approach, a cohort of 117 well-characterized ovarian cancer patients was assembled and ADAM17 levels in serum and corresponding ascitic fluid were determined at primary diagnosis. ADAM17 was quantified by enzyme-linked immunosorbent assay (ELISA). In the present study, ADAM17 was detected in the culture supernatant of ovarian cancer cell lines and primary cells. In addition, ADAM17 was found in serum and ascites of ovarian cancer patients. ADAM17 level was significantly increased in ovarian cancer patients compared to an age-matched control group (p < 0.0001). Importantly early FIGO I/II stages, which would not have been detected by CA-125, were associated with higher ADAM17 concentrations (p = 0.007). This is the first study proposing ADAM17 as a serum tumor marker in the setting of a gynecological tumor disease. Usage of ADAM17 in combination with CA-125 and other markers could help detect early stages of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: As for other neoplasms, liquid biopsy can be a useful tool to improve diagnosis and to monitor the response to therapy of high-grade serous epithelial ovarian cancer, which is the most common and lethal gynecological malignancy. In this paper, we provide an overview of the available knowledge on the current status and future opportunities by the analysis of tumor-derived components circulating in the blood of high-grade serous epithelial ovarian cancer patients. The lack of a sensitive and specific biomarker and the limits relating to the single primary tumor sampling make it difficult to monitor high-grade serous epithelial ovarian cancer (HGS-EOC) over time and to capture those alterations that are potentially useful in guiding clinical decisions. To overcome these issues, liquid biopsy has emerged as a very promising tool for HGS-EOC. The analysis of circulating tumor DNA appears to be feasible and studies assessing specific pathogenic mutations (i.e., TP53) or copy number alterations have shown a sufficient degree of sensitivity and specificity to be realistically used to monitor the effectiveness of antitumor therapy. Liquid biopsy can also provide potential important information on the mechanisms of sensitivity and resistance, e.g., by the determination of the reversion of BRCA mutations. Perspective studies are needed to test whether the application of liquid biopsy will significantly improve HGS-EOC management and patients' survival. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) accounts for 10% of all hematological malignancies, and it is the second most common hematological neoplasm for which chemotherapy is an important pharmacological treatment. High dose melphalan followed by autologous stem cell transplantation remains the standard of treatment for transplant-eligible patients with MM. In this review, we describe aspects of the pharmacokinetics and pharmacodynamics of melphalan therapy and related compounds. In addition, we describe the use of melphalan in innovative therapies for the treatment of MM, including the development of drug carriers to reduce systemic toxicity, combination therapy to improve the effectiveness of cancer therapy, and the chemical modification of the melphalan molecule to improve antitumor activity. [ABSTRACT FROM AUTHOR]

Background: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia can affect protein levels, but this has not been investigated on a larger scale. These effects could produce erroneous results in case-control studies if samples are not carefully matched. Methods: The proximity extension assay (PEA) was used to characterize 983 unique proteins in a total of 327 patients diagnosed with ovarian cancer and 50 age-matched healthy women. The samples were collected either at time of initial diagnosis or before surgery under general anaesthesia. Results: 421 of the investigated proteins (42.8%) showed statistically significant differences in plasma abundance levels comparing samples collected at time of diagnosis or just before surgery under anaesthesia. Conclusions: The abundance levels of the plasma proteome in samples collected before incision, i.e., after short-time fasting and under general anaesthesia differs greatly from levels in samples from awake patients. This emphasizes the need for careful matching of the pre-analytical conditions of samples collected from controls to cases at time of surgery in the discovery as well as clinical use of protein biomarkers. [ABSTRACT FROM AUTHOR]

The prognostic value of human leukocyte antigen (HLA) class I molecules in prostate cancer (PCa) remains unclear. Herein, we investigated the prognostic relevance of the most frequently expressed HLA-A alleles in Greece (A*02:01 and HLA-A*24:02) in de novo metastatic hormone-sensitive PCa (mPCa), which is a rare and aggressive disease characterized by a rapid progression to castration-resistance (CR) and poor overall survival (OS), contributing to almost 50% of PCa-related deaths. We identified 56 patients who had either progressed to CR (these patients were retrospectively analyzed for the time to the progression of CR and prospectively for OS) or had at least three months' follow-up postdiagnosis without CR progression and, thus, were prospectively analyzed for both CR and OS. Patients expressing HLA-A*02:01 showed poor clinical outcomes vs. HLA-A*02:01−negative patients. HLA-A*24:02−positive patients progressed slower to CR and had increased OS. Homozygous HLA-A*02:01 patients progressed severely to CR, with very short OS. Multivariate analyses ascribed to both HLA alleles significant prognostic values for the time to progression (TTP) to CR and OS. The presence of HLA-A*02:01 and HLA-A*24:02 alleles in de novo mPCa patients are significantly and independently associated with unfavorable or favorable clinical outcomes, respectively, suggesting their possible prognostic relevance for treatment decision-making in the context of precision medicine. [ABSTRACT FROM AUTHOR]

Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease. [ABSTRACT FROM AUTHOR]

The tumor microenvironment for epithelial ovarian cancer is complex and rich in bioactive molecules that modulate cell-cell interactions and stimulate numerous signal transduction cascades. These signals ultimately modulate all aspects of tumor behavior including progression, metastasis and therapeutic response. Many of the signaling pathways converge on the small GTPase Ras-related C3 botulinum toxin substrate (Rac)1. In addition to regulating actin cytoskeleton remodeling necessary for tumor cell adhesion, migration and invasion, Rac1 through its downstream effectors, regulates cancer cell survival, tumor angiogenesis, phenotypic plasticity, quiescence, and resistance to therapeutics. In this review we discuss evidence for Rac1 activation within the ovarian tumor microenvironment, mechanisms of Rac1 dysregulation as they apply to ovarian cancer, and the potential benefits of targeting aberrant Rac1 activity in this disease. The potential for Rac1 contribution to extraperitoneal dissemination of ovarian cancer is addressed. [ABSTRACT FROM AUTHOR]

Cancer–stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulated therapeutically. Results of emerging preclinical and clinical trials testing TME-modulating therapeutics for the treatment of OC are highlighted. [ABSTRACT FROM AUTHOR]