Search Results (1,645)

The ovary, as the primary organ responsible for reproduction and new life, plays a central role in female development, maturation, and health. Neoplasms arising from the ovary and its associated tissues exhibit substantial heterogeneity in their histopathological and molecular profiles, many of which remain poorly understood. This review aims to summarize recent advances in the understanding of genetic alterations underlying ovarian neoplasms and to explore therapeutic strategies informed by molecular biomarkers and tumor microenvironmental factors. A comprehensive literature search was performed, focusing on genomic alterations, biomarker-guided therapies, and tumor microenvironmental modulation in ovarian cancers. Emphasis was placed on studies addressing lipid mediator pathways and their roles in immune regulation and therapeutic response. Based on diagnostic classifications, recurrent alterations in TP53, MYC, PIK3CA, and KRAS are consistently observed across epithelial and germ cell ovarian tumors, whereas non-epithelial subtypes such as sex cord–stromal tumors (SCSTs) and small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), are predominantly associated with ARID1A and SMARCA4 mutations, respectively. These findings highlight distinct pathogenic mechanisms linked to specific genetic alterations and reveal potential therapeutic vulnerabilities. Moreover, lipid metabolism has been closely implicated in immune surveillance through STING signaling cascades within innate immune cells, suggesting that lipid mediators and their associated genes may represent promising therapeutic targets in ovarian cancers (OCs). Targeting lipid mediators could be particularly effective in relapsed OCs, as modulating innate immune cells within the tumor microenvironment (TME) may enhance immune surveillance and improve antitumor responses. Integrating genetic and microenvironmental insights offers a promising direction for developing more effective and personalized therapeutic strategies in OC. Full article

Background: Muscle-invasive bladder cancer (MIBC) represents a highly aggressive malignancy associated with significant morbidity and mortality. The current standard treatment, which includes radical cystectomy and platinum-based chemotherapy, is burdened by high toxicity and a substantial risk of relapse. For this reason, over the past decade, novel therapeutic strategies involving immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and targeted therapies have been investigated. This review aims to summarize current clinical evidence and ongoing trials evaluating these approaches in the perioperative setting. Methods: A systematic search was conducted using PubMed, EMBASE, and Cochrane databases, along with abstracts from major oncology conferences (ASCO, ESMO, SGO). Clinical trials assessing ICIs, ADCs, and targeted therapies, either alone or in combination with each other or with chemotherapy, in MIBC, were included. Results: Several early-phase and phase III trials have investigated the perioperative management of MIBC. Various studies evaluated the addition of ICIs to standard chemotherapy, demonstrating promising results in terms of pathological complete response. In parallel, the encouraging outcomes with ICIs and ADCs alone in the neoadjuvant or adjuvant setting paved the way for their combination in integrated strategies. Biomarker-driven approaches, based on circulating tumor DNA and specific genomic alterations, are being actively explored to improve patient selection and personalize treatment. Conclusions: ICIs, ADCs, and targeted therapies are reshaping the therapeutic landscape of MIBC. While early results are promising, further data and biomarker validation are essential to establish their definitive role and guide clinical decision-making in the perioperative setting. Full article

Background: Chemotherapy, targeted therapy and radiotherapy are the cornerstones of cancer treatment. However, therapeutic resistance—not only to these classic modalities but also to novel therapeutics like immune checkpoint inhibitors (ICIs) and antibody-drug conjugates—remains a major hurdle. Resistance significantly limits efficacy and increases recurrence rates. A deep understanding of the molecular mechanisms driving this resistance is critical for developing personalized therapeutic strategies and improving patient outcomes. Recent Advances: Patient-derived cancer organoids have emerged as a powerful preclinical platform that faithfully recapitulates the genetic, phenotypic, and histological characteristics of original tumors. Consequently, PDOs are being widely utilized to evaluate drug responses, investigate resistance mechanisms, and discover novel therapeutic targets for a range of therapies. Limitations: While organoid models have been instrumental in studying resistance, significant limitations persist. First, standard organoid-only models lack key tumor microenvironment components, such as immune cells, limiting immunotherapy research. Second, there is a significant lack of research on acquired resistance, particularly in lung cancer. This gap is largely driven by the clinical infeasibility of rebiopsy in patients with progressive diseases. Third, the absence of standardized protocols for generating and validating resistance models hinders reproducibility and complicates clinical translation. Conclusions: This review summarizes recent advances in using organoid models to study resistance to chemotherapy, radiotherapy, and novel therapeutics (ICIs and ADCs). We emphasize the critical need for standardization in resistance organoid research. We also propose future directions to overcome existing challenges, including the integration of co-culture systems (to include the TME) and advanced technologies (e.g., scRNA-seq, Spatial Transcriptomics). Our specific focus is on advancing lung cancer resistance modeling to enable functional precision medicine. Full article

While the distinct roles of lymphocyte populations are well characterized in adaptive immunity, the phenotypic and functional diversity of innate immune cells is less explored. In recent years, subsets of monocytes have gained attention, as prominent shifts in population frequencies have been observed in disease states such as cancer. This narrative review summarizes current knowledge of the distribution and functional differences among the three major monocyte subsets (classical, intermediate, non-classical) in tumor settings. It includes rare populations, such as neutrophil-like, CD56+, and Tie2-expressing monocytes. Scientific evidence indicates that the phenotypical and functional heterogeneity of monocyte subsets determines their roles in either preventing cancer development or supporting the progression of disease through a remarkable diversity of mechanisms. Of note, alterations in the distribution of monocyte subsets and their functional reprogramming have been identified as drivers of cancer progression. While changes in monocyte frequencies have limited diagnostic biomarker potential for cancer detection, they may reflect the progression of disease and response to therapy. Based on subset-specific properties, distinct monocyte populations are increasingly recognized as promising targets of cancer immunotherapy. Yet novel strategies targeting monocyte populations must consider the risk of treatment reversal given the high plasticity of these cells. Full article

The high attrition rates in glioblastoma (GB) therapeutic development stem largely from preclinical models that fail to adequately recapitulate the dynamic tumor–host ecosystem. Unlike previous reviews that characterize glioma cell lines in isolation, this article integrates tumor biology with the distinct neuro-immune–endocrine landscapes of major laboratory rat strains. We critically evaluate standard rat malignant glioma cell lines (C6, F98, RG2, 9L) alongside transplantable tissue models (GB 101.8, GB 15/47), which offer enhanced translational relevance, demonstrating that the predictive value of any model is contingent upon the specific “glioma model and host strain” pairing and the individual physiological characteristics of the host. We provide evidence that strain-specific hypothalamic–pituitary–adrenal (HPA) axis reactivity (e.g., hyper-reactive Fischer 344 versus normo-reactive Wistar) acts as a decisive, yet often overlooked, modulator of the tumor microenvironment and therapeutic response. The review delineates the utility and limitations of these models, specifically addressing the MHC incompatibilities of the widely used C6 model in immunotherapy research, while contrasting it with the immune-evasive phenotypes of RG2 and the GB 101.8 tissue model. Furthermore, we highlight the superiority of tissue transplants in preserving cellular polyclonality and diffuse infiltration patterns compared to the circumscribed growth often observed in cell line-derived tumors. Consequently, we propose a strategic selection paradigm wherein immunogenic models serve as bioindicators of host immunocompetence, while invasive, non-immunogenic systems (F98, RG2, and GB 101.8) are utilized to investigate therapeutic resistance and systemic host-tumor interactions. Full article

Background/Objectives: Tumor cells exploit a variety of mechanisms to inhibit the immune response to lung cancer. The programmed cell death protein-1/programmed death-ligand-1 (PD-1/PD-L1) axis is frequently dysregulated in lung cancers with significant impacts on tumor growth. A sex difference has been observed in lung cancer progression and the response to PD-1/PD-L1 therapy, with the extent of benefits differing between men and women. The mechanism underlying these differences has not been fully established. Methods: In an attempt to better understand the nature of these differences, we searched the available literature for reports connecting sex specific bioactive molecules—including estrogens, progesterone, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, leptin, and activin/inhibin—to sex differences in lung cancer and the response to PD-1/PDL-1 therapies. We then condensed this information to help generate testable hypotheses to explain the observed sex differences in lung cancer and its immunotherapies. Conclusions: From these efforts, we discovered potential roles for sex steroids, FSH, LH, prolactin, leptin, and activin/inhibin in both immune cell activity and cancer cell survival and in the response to PD-1/PD-L1 therapies. Full article

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail. Full article

Cancer remains a major global health burden driven by genetic, metabolic, and microenvironmental alterations. Although reactive oxygen species (ROS) and oxidative stress have long been implicated in cancer biology, current understanding remains fragmented and, in several areas, conceptually disputed considering how ROS and oxidative stress thresholds determine the switch between tumor-promoting signaling and cytotoxic outcomes, and whether redox-based therapies can be safely and selectively applied across different cancer types. Moreover, existing studies often examine isolated pathways or single ROS, leaving unanswered the question of how spatial and temporal ROS dynamics and oxidative stress responses shape carcinogenesis, metastasis, and therapeutic resistance. This review moves beyond descriptive summarization by critically examining unresolved mechanistic gaps, including (i) how ROS and oxidative stress interact with epigenetic and metabolic reprogramming, (ii) the context-dependent role of ROS-driven oxidative stress within the tumor microenvironment and immune evasion, and (iii) why ROS-targeting and oxidative stress-modulating therapies have shown inconsistent clinical translation despite promising preclinical data. We highlight areas of consensus as well as conflicting evidence, synthesizing recent advances across multiple cancer types to clarify where ROS and oxidative stress function as drivers, modulators, or vulnerabilities. Finally, we outline emerging research priorities, such as real-time redox profiling, subtype-specific targeting strategies, and combination approaches, to guide the development of more precise and effective ROS- and oxidative-stress-based interventions. Full article

Background/Objectives: Melanoma is a highly malignant skin tumor with poor response to conventional chemotherapeutic regimens. Melanoma cells induce cytotoxic T cell-mediated immune responses, and immunotherapy has significantly improved survival rates for patients with advanced disease. Methods: Here, we investigate NK cell-mediated melanoma cell killing and its regulation by PD-L1/PD-1 blockade and IFNβ. Four melanoma cell lines were used in this study. To evaluate NK cell cytotoxicity, cells were exposed to NK cells with or without IFNβ. The calcein release assay was used to measure cell death, while specific inhibitors and siRNA silencing were applied to determine the contribution of individual effector pathways. Results: NK cells were able to kill melanoma cells with sensitivity to killing varying between different cell lines. Cytotoxic effects were mainly mediated through activation of the TRAIL signaling cascade. In cell lines with low sensitivity to NK cell killing, expression of PD-L1 was noted and killing by NK cells could be significantly increased by inhibition of the PD-L1/PD-1 checkpoint. Killing of melanoma cells could be further increased by incubation of NK cells with IFNβ. Conclusions: Our results point to a role of NK cells in the killing of melanoma cells and a potential clinical benefit of a combination therapy of IFNβ and anti-PD-1 antibody. Full article

Hepatocellular carcinoma (HCC) remains a prevalent form of cancer with a poor prognosis and requires systemic therapies for most advanced cases. In this review, we summarize considerations for selecting treatment options for HCC, particularly with regard to immune checkpoint inhibitors (ICIs). Traditional chemotherapy has been surpassed by molecular-targeted therapies and ICIs, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors, which enhance the immune response against tumors. The European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines recommend atezolizumab/bevacizumab (Atez/Bev) and tremelimumab/durvalumab (Dur/Tre) as first-line treatments for unresectable HCC, along with alternatives, such as sorafenib and lenvatinib. Atezolizumab and bevacizumab have demonstrated superior efficacy but require the monitoring of bleeding risk and adverse events, such as proteinuria. Tremelimumab and durvalumab offer alternatives for patients at high risk of anti-Vascular Endothelial Growth Factor (anti-VEGF)-related complications. In cases where ICIs are contraindicated, lenvatinib and sorafenib serve as additional options, with lenvatinib demonstrating longer progression free survival (PFS) in clinical trials. It is important to consider that each treatment has specific side effects or contraindications, and the choice of medication should be based not only on the therapeutic efficacy of the drug, but also on the patient’s health status, liver function, and tumor characteristics. Full article

Background: Antibodies have the unique ability to recognize antigens and to be recognized as antigens by other antibodies, creating a balanced network that regulates the humoral part of the immune system. An antibody that uniquely identifies another antibody of a given specificity as its antigen is referred to as an anti-idiotypic antibody. Methods: A descriptive literature review was conducted using the PubMed database, including publications up to 2025. Results: This review examines the formation mechanisms of anti-idiotypic antibodies, their functional attributes, and their importance in diverse pathologies. A key focus is their capacity to neutralize pathogenic autoantibodies, offering a novel strategy for treating autoimmune diseases. Conversely, the generation of anti-Id Abs against therapeutic monoclonal antibodies (anti-drug antibodies) represents a significant challenge for biologic therapy, a complication addressed in a dedicated section on detection methods. Furthermore, consideration is given to the application of anti-Id Abs as innovative tools for vaccine design, particularly in oncology. By mimicking tumor-associated antigens, anti-Id Abs can induce a potent, targeted immune response against cancer with minimal side effects, presenting an alternative to conventional chemotherapy and radiation. Conclusions: Anti-Id Abs hold significant therapeutic promise. Their ability to selectively suppress pathogenic autoantibodies allows for precise immune intervention without broad immunosuppression. Additionally, their utility extends to vaccine development for various diseases. Further research into anti-Id Abs will deepen our understanding of immune regulation and open new avenues for targeted therapies. Full article

The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development. Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression. We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies. Full article

Immunotherapy has demonstrated significant efficacy in colorectal cancer (CRC), but its therapeutic effects remain limited in microsatellite stable (MSS) patients, indicating the critical role of the tumor immune microenvironment (TIME) in regulating immune responses. Lipid rafts, dynamic membrane microdomains enriched in cholesterol and sphingolipids, have emerged as potential targets for TIME remodeling through their integration of immune signal transduction, enrichment of cell death receptors, and regulation of immune cell functionality. This review outlines the pivotal mediating roles of lipid rafts in cellular survival, death, and tumor progression. Specifically, MSS-type CRC exhibits lipid raft structural remodeling driven by dysregulated lipid metabolism, which fosters multiple immune escape mechanisms through exosome-mediated immunosuppressive signaling, promotion of tumor-associated macrophage (TAM) M2 polarization, enhanced infiltration of regulatory T cells (Tregs), and functional exhaustion of effector cells, such as CD8⁺ T cells and NK cells. Finally, we discuss targeted therapeutic strategies based on lipid raft characteristics and CRC molecular profiles, proposing an innovative multidimensional treatment framework combining immune checkpoint inhibitors with lipid raft-targeted interventions and chemoradiotherapy. This approach provides theoretical and strategic support for overcoming CRC immunotherapy resistance and advancing clinical translation. Full article

Despite advances in blood-based screening tests for colorectal cancer (CRC), most existing assays focus on DNA-based biomarkers, which predominantly reflect tumor-derived fragments released at later disease stages. In contrast, whole-blood transcriptomic profiling can capture systemic immune responses and tumor–host interactions, offering a complementary strategy for earlier disease detection. However, clinically validated whole-blood transcriptomic signatures remain limited. Here, we investigated a whole-blood RNA-based biomarker discovery strategy by integrating multi-cohort transcriptomic resources. Public GEO datasets (GSE164191 and GSE11545) were harmonized and analyzed, yielding 956 differentially expressed genes (DEGs). Multi-layer biological filtering incorporating PPI networks, transcription factors, CRC-related GWAS variants, whole-blood eQTL signals, DigSeE, and CoReCG disease associations refined these to 375 high-confidence transcripts (WB-PADs). In parallel, RNA-seq analysis of a Korean cohort (10 CRC vs. 10 controls) identified 217 DEGs (WB-K). Cross-dataset convergence highlighted seven overlapping transcripts, and five candidates (DLG5, CD177, SH2D1B, NQO2, and KRT73) were selected for validation. RT-qPCR in an independent clinical cohort (106 CRC and 123 healthy controls) confirmed four transcripts with significant discriminatory ability. A multivariable logistic regression model derived from the five-transcript signature achieved an AUC of 0.952 (95% CI 0.884–1.000), with sensitivities of 0.889 and 0.667 at fixed specificities of 90% and 95%, respectively, demonstrating strong applicability for screening-relevant thresholds. Notably, the model retained high accuracy in early-stage CRC (Stage I–II: AUC 0.929, 95% CI 0.868–0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection. Full article

High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) and specific shared neoantigens (H3.3K27M). Crucially, we highlight pivotal data from the PNOC007 trial, where the magnitude of H3.3K27M-specific T-cell expansion correlated directly with significantly longer overall survival (OS), establishing a causal link between pharmacodynamics and clinical benefit. However, the unique challenges of the immunosuppressive tumor microenvironment and the detrimental effect of necessary corticosteroids remain paramount barriers. Future success relies on multi-modal combination strategies, the development of next-generation personalized neoantigen vaccines, and the application of advanced neuroimaging to accurately assess treatment response. Full article