Search Results (215)

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy characterized by intraperitoneal spread and chemotherapy resistance. Chemotherapies have demonstrated limited effectiveness in HGSOC, underscoring the urgent need to evaluate how the tumor microenvironment (TME) was reshaped by chemotherapy in different sites of tumor foci. In this study, we performed single-cell transcriptomic analysis to explore the TME in samples obtained from various sites of tumor foci, with or without the history of Neoadjuvant chemotherapy (NACT). We discovered that chemotherapy reshaped the tumor immune microenvironment, evident through the reduction in human leukocyte antigen (HLA) diversity and the increase in PDCD1/CD274 in CD8_ANXA1, LAMP3+ dendritic cell (DC_LAMP3), and EREG+ monocytes (mono_EREG). Moreover, cancer.cell.2, cancer-associated C3+ fibroblasts (CAF_C3), and Fibrocyte_CD34, which are prone to accumulate in the metastatic site and post-NACT group, harbored poor clinical outcome, reflected in the immune exclusion and tumor progression signaling. Cell–cell communication identified a stronger interaction between cancer.cell.2 and CAF_C3, as well as Fibrocyte_CD34, in post-NACT samples, indicating that chemotherapy reshapes pre-existing cell clusters in a site-dependent manner. Our findings suggest that chemotherapy and sites of foci were critical for the transcriptional reprogramming of pre-existed cell clusters. Our study offers a single-cell phenotype data substrate from which to develop a personalized combination of chemotherapy and immunotherapy. Full article

The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options—including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as immunotherapy. While these advances have markedly improved patient outcomes, they also introduce challenges related to implementation, monitoring, and resource allocation. Notably, therapies like CDK4/6 inhibitors require particularly close monitoring, creating logistical and capacity challenges for medical oncologists, whose workloads are already stretched due to rising cancer incidence and treatment complexities. These challenges underscore the need for innovative care delivery solutions to ensure patients with EBC continue to receive optimal care. This paper offers a comprehensive guide—a playbook—of multidisciplinary-team-based care models designed to optimize adjuvant treatment delivery in EBC. Drawing on real-world evidence and successful applications across Canadian centers, we explore models led by nurses, nurse practitioners (NPs), general practitioners in oncology (GPO), and pharmacists. Each model leverages the unique expertise of its team to manage treatment toxicities, facilitate adherence, and enhance patient education, thereby promoting effective and sustainable care delivery. Importantly, these models are not intended to compete with one another, but rather to serve as a flexible recipe book from which breast cancer care teams can draw strategies tailored to their local resources and patient needs. By detailing implementation strategies, benefits, and challenges—in many instances supported by quantitative metrics and economic evaluations—this work aims to inspire care teams nationwide to optimize the adjuvant management of patients with HR+, HER2– EBC. Full article

Ovarian cancer is a leading cause of cancer-related deaths among women, with platinum resistance posing a significant challenge. Conventional therapies often fail in these cases, highlighting the urgent need for novel treatment approaches. Immunotherapy has emerged as a promising strategy, offering renewed hope for patients with platinum-resistant ovarian cancer (PROC). This review explores the current landscape of immunotherapies for PROC, discussing different approaches, their mechanisms of action, and the potential for overcoming the limitations of conventional treatments. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Mucin, a heavily glycosylated glycoprotein, serves an important function in forming protective and immune defense barriers against the exterior environment on epithelial surfaces. While secreted-type mucins are involved in mucous production, transmembrane mucins, which contain O-glycosylated tandem repeats, play a pivotal role in cellular signaling, especially in immune modulation and mediating inflammatory response. However, dysregulation in mucin expressions, such as MUC1, MUC2, MUC4, MUC5AC, and MUC16, have been observed in many cancer cells. More specifically, alterations in the expression and glycosylation of MUC1 have been associated with the upregulation of pathways involving the cell proliferation, angiogenesis, migration, and invasion of cancer cells. With mucin’s extensive involvement in cancer biology, several mucin biomarkers, such as CA125, CA19-9, and CEA, have been utilized as diagnostic and prognostic monitoring biomarkers in ovarian, pancreatic, and colon cancer. Vaccines and antibody therapy against abnormal mucin glycosylation have also been investigated for potential therapy for mucin-related cancers that are resistant to traditional chemotherapy agents. Despite the lack of specificity in mucin biomarkers and challenges in efficient drug delivery systems, the current advancement in mucin-targeted immunotherapy highlighted the pivotal potential in developing therapeutic targets to improve cancer prognosis. Full article

Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators of host–microbe interactions, profoundly influencing cancer biology. These nanoscale vesicles, produced by both Gram-positive and Gram-negative bacteria, carry diverse biomolecular cargo such as proteins, lipids, nucleic acids, and metabolites. BEVs play dualistic roles in tumor promotion and suppression by modulating the tumor microenvironment, immune responses, and genetic regulation. This review synthesizes the current understanding of BEVs in various cancers, including gastrointestinal, ovarian, breast, lung, brain, and renal malignancies. BEVs are highlighted for their potential as diagnostic biomarkers, prognostic indicators, and therapeutic agents, including their applications in immunotherapy and advanced engineering for precision medicine. Challenges such as heterogeneity, standardization, and clinical scalability are critically analyzed, with case examples providing actionable insights. Future directions emphasize interdisciplinary collaborations, emerging technologies, and the integration of BEV-based tools into clinical workflows. This review underscores the transformative potential of BEVs in advancing cancer diagnostics and therapeutics, paving the way for innovations in precision oncology. Full article

Background: Ovarian cancer (OC) is characterized by high incidence and mortality rates; however, due to its immunologically “cold” phenotype, the effectiveness of immunotherapy as a strategy for OC remains inadequate. Although the FAM111B gene promotes the progression of various solid tumors, its specific function within the tumor immune microenvironment (TIME) of OC remains unclear. Methods: This study used multiplex immunofluorescence techniques and bioinformatics analysis to examine the role of FAM111B within the TIME of OC. Through multiplex immunofluorescence, we assessed the protein expression levels of FAM111B alongside key immune cell markers, including FOXP3, CD4, CD8, CD68, CD163, CD66b, and CD11c. Furthermore, we employed bioinformatics methods using The Cancer Genome Atlas database to validate FAM111B function at the mRNA level in OC. Results: We observed a positive correlation between FAM111B expression and immune cell infiltration, including T cells, macrophages, and dendritic cells. FAM111B, M2 macrophages, and regulatory T cells were associated with poorer overall survival in OC patients. Additionally, specific T cell subsets and dendritic cells were correlated positively with programmed death-ligand 1 expression, while FAM111B levels were linked to multiple immune checkpoint molecules. Conclusions: This study reveals a positive correlation between FAM111B overexpression and the infiltration levels of immune cells in OC. In OC patients characterized by elevated FAM111B expression, the potential augmentation of immune cell infiltration within the TIME may consequently enhance the efficacy of immunotherapy. Full article

Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetics. Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with in silico follow-up. Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with p < 5 × 10⁻⁸ associated with at least one of the cancer types at p < 10⁻³ and one of the autoimmune/autoinflammatory diseases at p < 10⁻³. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping led variants to nearest genes as putative functional targets and focusing on immune-related genes implicated 32 genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1, IKZF1, SPI1, SH2B3, LAT) was each strongly correlated (Spearman’s ρ > 0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4, CD8A, CD11B, CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via the expression of quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable. Conclusions: We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded by IRF1, IKZF1, SPI1, SH2B3 and LAT as possible targets for cancer immunotherapy. Full article

Background/Objectives: Ovarian cancer remains one of the most commonly diagnosed malignancies among women worldwide. The heterogeneity among tumor subtypes and the emergence of treatment resistance have raised significant concerns regarding the long-term efficacy of chemotherapy, radiotherapy, and immunotherapy. In response to these challenges, drug repurposing strategies—utilizing existing drugs in novel therapeutic contexts—have gained increasing attention. This study aimed to investigate the cytotoxic and apoptotic effects of the combined application of doxorubicin (DX) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3). Methods: OVCAR3 cells were cultured in RPMI medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Cell viability and proliferation were assessed using the MTT assay following treatment with various concentrations of DX and TQ. NucBlue immunofluorescence staining was employed to examine nuclear morphology and to identify apoptosis-associated changes. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was per-formed to evaluate the expression levels of apoptosis-related and oncogenic pathway genes, including RAF, RAS, Bcl-2, and Bax. Results: The results demonstrated that the combination of DX and TQ significantly reduced OVCAR3 cell viability and induced apoptosis in a dose-dependent manner. qRT-PCR analysis revealed a downregulation of RAS, RAF, and Bcl-2 expression, along with an upregulation of Bax, indicating activation of the intrinsic apoptotic pathway. These findings suggest that thymoquinone exerts an-ti-proliferative and pro-apoptotic effects by modulating the RAS/RAF signaling cascade. Furthermore, the co-administration of thymoquinone with doxorubicin potentiated these effects, suggesting a synergistic interaction between the two agents. Conclusions: Histopathological and molecular evaluations further confirmed the activation of apoptosis and the suppression of key oncogenic pathways. Collectively, these results underscore the therapeutic potential of thymoquinone as both a monotherapy and an adjuvant to conventional chemotherapy, warranting further validation in preclinical and clinical studies. Full article

Background/Objectives: Artificial intelligence (AI) is increasingly influencing oncological research by enabling precision medicine in ovarian cancer through enhanced prediction of therapy response and patient stratification. This systematic review and meta-analysis was conducted to assess the performance of AI-driven models across three key domains: genomics and molecular profiling, radiomics-based imaging analysis, and prediction of immunotherapy response. Methods: Relevant studies were identified through a systematic search across multiple databases (2020–2025), adhering to PRISMA guidelines. Results: Thirteen studies met the inclusion criteria, involving over 10,000 ovarian cancer patients and encompassing diverse AI models such as machine learning classifiers and deep learning architectures. Pooled AUCs indicated strong predictive performance for genomics-based (0.78), radiomics-based (0.88), and immunotherapy-based (0.77) models. Notably, radiogenomics-based AI integrating imaging and molecular data yielded the highest accuracy (AUC = 0.975), highlighting the potential of multi-modal approaches. Heterogeneity and risk of bias were assessed, and evidence certainty was graded. Conclusions: Overall, AI demonstrated promise in predicting therapeutic outcomes in ovarian cancer, with radiomics and integrated radiogenomics emerging as leading strategies. Future efforts should prioritize explainability, prospective multi-center validation, and integration of immune and spatial transcriptomic data to support clinical implementation and individualized treatment strategies. Unlike earlier reviews, this study synthesizes a broader range of AI applications in ovarian cancer and provides pooled performance metrics across diverse models. It examines the methodological soundness of the selected studies and highlights current gaps and opportunities for clinical translation, offering a comprehensive and forward-looking perspective in the field. Full article

Mesothelin (MSLN), a glycoprotein-based tumor antigen, is elevated in several malignancies and it is related to a poor prognosis, as it enhances tumor aggression, dissemination and chemotherapy resistance. MSLN plays a crucial role in epigenetic and signal pathway regulation and it can be an important biomarker. MSLN targeting is in particular, associated with CA125/MUC16, which offers the potential to improve lung, pancreatic, colon and ovarian cancer detection as well as therapeutic strategies. MSLNtargeted therapies have shown favorable results, such as CAR NK cells, 227Th conjugate and CAR-T cells, which target mesothelin. Significant advancements can be achieved with novel techniques, such as mesothelin-targeting BiTEs and simultaneous CAR-T cells. Immunotherapies targeting mesothelin have the potential to completely transform the way cancer is therapy in patients with limited options. To fully comprehend the mechanisms of MSLN, more investigation is required to explore its role in cancer for improved patient outcomes. The complex control, cellular functions and clinical significance of MSLN in the advancement of cancer are highlighted in this review.  Full article

Pharmacogenomics, the study of how genetic variations influence drug response, has become integral to cancer treatment as personalized medicine evolves. This review aims to explore key pharmacogenomic biomarkers relevant to cancer therapy and their clinical implications, providing an updated and comprehensive perspective on how genetic variations impact drug metabolism, efficacy, and toxicity in oncology. Genetic heterogeneity among oncology patients significantly impacts drug efficacy and toxicity, emphasizing the importance of incorporating pharmacogenomic testing into clinical practice. Genes such as CYP2D6, DPYD, UGT1A1, TPMT, EGFR, KRAS, and BRCA1/2 play pivotal roles in influencing the metabolism, efficacy, and adverse effects of various chemotherapeutic agents, targeted therapies, and immunotherapies. For example, CYP2D6 polymorphisms affect tamoxifen metabolism in breast cancer, while DPYD variants can result in severe toxicities in patients receiving fluoropyrimidines. Mutations in EGFR and KRAS have significant implications for the use of targeted therapies in lung and colorectal cancers, respectively. Additionally, BRCA1/2 mutations predict the efficacy of PARP inhibitors in breast and ovarian cancer. Ongoing research in polygenic risk scores, liquid biopsies, gene–drug interaction networks, and immunogenomics promises to further refine pharmacogenomic applications, improving patient outcomes and reducing treatment-related adverse events. This review also discusses the challenges and future directions in pharmacogenomics, including the integration of computational models and CRISPR-based gene editing to better understand gene–drug interactions and resistance mechanisms. The clinical implementation of pharmacogenomics has the potential to optimize cancer treatment by tailoring therapies to an individual’s genetic profile, ultimately enhancing therapeutic efficacy and minimizing toxicity. Full article

Ovarian cancer is the fifth leading cause of cancer-related death among women, which is one of the most common gynecological cancers worldwide. Although several cytoreductive surgeries and chemotherapies have been attempted to address ovarian cancer, the disease still shows poor prognosis and survival rates due to prevalent metastasis. Peritoneal metastasis is recognized as the primary route of metastatic progression in ovarian cancer. It causes severe symptoms in patients, but it is generally difficult to detect at an early stage. Current anti-cancer therapy is insufficient to completely treat metastatic ovarian cancer due to its high rates of recurrence and resistance. Therefore, developing strategies for treating metastatic ovarian cancer requires a deeper understanding of the tumor microenvironment (TME) and the identification of effective therapeutic targets through precision oncology. Given that various signaling pathways, including TGF-β, NF-κB, and PI3K/AKT/mTOR pathways, influence cancer progression, their activity and significance can vary depending on the cancer type. In ovarian cancer, these pathways are particularly important, as they not only drive tumor progression but also impact the TME, which contributes to the metastatic potential. The TME plays a critical role in driving metastatic features in ovarian cancer through altered immunologic interactions. Recent therapeutic advances have focused on targeting these distinct features to improve treatment outcomes. Deciphering the complex interaction between signaling pathways and immune populations contributing to metastatic ovarian cancer provides an opportunity to enhance anti-cancer efficacy. Hereby, this review highlights the mechanisms of signaling pathways in metastatic ovarian cancer and immunological interactions to understand improved immunotherapy against ovarian cancer. Full article

Background/Objectives: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have revolutionized cancer immunotherapy, however the clinical relevance of their soluble forms (sPD-1 and sPD-L1) remains less studied. Soluble PD-1 and PD-L1 have been implicated in tumor progression, prognosis, and treatment response across various malignancies. This study aims to provide a comprehensive analysis of sPD-1 and sPD-L1 levels in serum across diverse tumor types, including rare malignancies, and to evaluate their associations with clinicopathological characteristics and prognostic significance. Methods: In this study we analyzed sPD-1 and sPD-L1 levels in serum samples from 675 cancer patients representing a range of malignancies, including ovarian cancer, breast cancer, gastric cancer, colorectal cancer, renal cell carcinoma, and bone tumors. sPD-1 and sPD-L1 concentrations were measured using ELISA. Statistical analyses were performed to evaluate associations between soluble marker concentrations and clinicopathological factors, including tumor stage, size, histological subtype, and survival outcomes. Results: Elevated sPD-L1 levels were observed in several tumor types, including ovarian cancer, renal cell carcinoma, and gastric cancer, where they were associated with features of advanced disease, such as tumor size, stage, and metastases. In contrast, sPD-1 levels showed limited associations, with significant findings solely in gastric cancer and bone tumors, where levels correlated with histological subtype and differentiation. Prognostic analyses identified sPD-L1 as a marker of poor survival outcomes in ovarian cancer and bone tumors, while sPD-1 displayed no consistent prognostic significance. Conclusions: This study identifies the potential of sPD-L1 as a biomarker for tumor progression and prognosis across multiple malignancies. In contrast, sPD-1 showed limited clinical relevance, suggesting the importance of further investigation. These findings contribute to our understanding of soluble immune checkpoint proteins and their integration into personalized oncology strategies. Full article