Seminars In Oncology[JOURNAL]
Sun
200 papers
Prognostic significance and therapeutic potential of pyroptosis in gynecological malignancies.
Wei Z, Liu HH, Yun Y … +5 more , Yuan HY, Ding Y, Chen Y, Liu YN, Li SS
Semin Oncol · 2026 Apr · PMID 41832821 · Publisher ↗
BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death, has emerged as a critical regulator of tumor biology. Its prognostic value in gynecologic malignancies remains unclear. METHODS: We performed a revie...
BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death, has emerged as a critical regulator of tumor biology. Its prognostic value in gynecologic malignancies remains unclear. METHODS: We performed a review of studies evaluating pyroptosis-related targets (PRTs) in ovarian, cervical, and endometrial cancers. Eligible studies were identified through multiple databases up to August 31, 2025. Data extraction and quality assessment were conducted independently by two reviewers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to determine the association between PRT expression and survival outcomes. RESULTS: 16 studies involving 19 PRTs met the inclusion criteria. Inhibitory PRTs were significantly associated with poor prognosis (HR = 1.52, 95% CI: 1.41-1.63), whereas enhancing PRTs correlated with favorable survival (HR = 0.89, 95% CI: 0.81-0.99). The overall trends remained consistent across different study characteristics, with heterogeneity largely influenced by variations in expression levels, cancer types, and detection methods. Sensitivity analyses confirmed the robustness of findings, although publication bias was detected in the inhibitory group. CONCLUSION: This study provides the first systematic evidence that PRTs hold prognostic significance in gynecologic malignancies. Pyroptosis appears to function as a tumor-suppressive mechanism, supporting its role as a prognostic biomarker and potential therapeutic target. Large-scale, multicenter, and mechanistic studies are warranted to validate and expand these findings.
Ferroptosis in ovarian cancer: Regulation, immunity, and therapeutic potential with the tumor microenvironment.
Jiang R, Yu Y, Guan J … +7 more , Ma J, Qiu H, Zhong J, Liu N, Zhao H, Zheng Y, Du Y
Semin Oncol · 2026 Apr · PMID 41759227 · Publisher ↗
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a pivotal and translationally promising target in ovarian cancer management. This review systematically explores the du...
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a pivotal and translationally promising target in ovarian cancer management. This review systematically explores the dual role of ferroptosis in inhibiting tumor growth while simultaneously promoting immune evasion and cancer recurrence. We synthesize current evidence on the dynamic interplay between ferroptosis, tumor progression, and the immunosuppressive tumor microenvironment in ovarian cancer. We highlight key biological features of ovarian cancer, including its iron-rich ascites and lipid-abundant omentum, create a unique context for ferroptosis modulation. Crucially, ferroptosis not only influences cancer cell survival and chemoresistance but also profoundly shapes antitumor immunity by affecting T cell function, macrophage polarization, and dendritic cell activity. We discuss how targeting ferroptosis through inducers, nanoparticle delivery systems, or combination with PARPi and immunotherapy can overcome cisplatin and PARPi resistance and reverse immunosuppression. Despite clinical challenges such as heterogeneity and recurrent disease, ferroptosis-related gene signatures and emerging noninvasive detection methods offer avenues for patient stratification. We conclude that integrating ferroptosis-targeted strategies into the therapeutic arsenal holds significant potential to improve outcomes for ovarian cancer patients.
Advances in the management of metastatic lobular breast cancer: Current evidence and emerging treatments.
Martín-Quesada AI, Martín-Abreu C
Semin Oncol · 2026 Apr · PMID 41740233 · Publisher ↗
Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positi...
Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positivity, low-to-intermediate proliferation, and atypical metastatic spread to bone and gastrointestinal/peritoneal sites. Diagnostic assessment is often challenging owing to diffuse infiltration, frequently yielding non-measurable disease per response evaluation criteria in solid tumors (RECIST). Molecularly, ILC is enriched for phosphoinositide 3-kinase (PI3K) activation and harbors emerging vulnerabilities-such as ROS1 synthetic lethality in CDH1-deficient tumors and fibroblast growth factor receptor 1 (FGFR1)/bromodomain and extra-terminal (BET) dependencies-now under study. Because metastatic ILC remains underrepresented in trials, systemic therapy often mirrors invasive ductal carcinoma (IDC). This short communication synthesizes current evidence to distinguish shared from plausibly lobular-specific signals; highlights near-term opportunities-including antibody-drug conjugates (ADCs), oral selective ER degraders (SERDs), and selective use of immunotherapy in an immune-enriched subset with higher tumor-infiltrating lymphocytes (TILs) and PD-L1; and outlines trial-design adaptations-such as incorporating 18F-fluoroestradiol PET (FES-PET)-to improve representation and interpretability in metastatic ILC research.
DNA methylation-mediated extracellular matrix gene silencing in colorectal cancer.
Menyhart O, Müller D, Győrffy B
Semin Oncol · 2026 Apr · PMID 41707499 · Publisher ↗
Epigenetic alterations, particularly DNA methylation, play a crucial role in colorectal cancer (CRC) development and progression. We aimed to investigate DNA methylation changes across normal colon samples, adenomas, and...
Epigenetic alterations, particularly DNA methylation, play a crucial role in colorectal cancer (CRC) development and progression. We aimed to investigate DNA methylation changes across normal colon samples, adenomas, and adenocarcinomas to identify critical gene networks associated with disease progression. We conducted a comprehensive DNA methylation analysis on 2,346 samples. We extracted CRC methylation data of normal colon mucosa, adenomas, and adenocarcinomas from the genomic data commons data portal and the gene expression omnibus. We ranked differentially methylated genes by their area under the ROC curve (AUC) and retained those with AUC ≥ 0.91. Pathway enrichment analyses determined significantly impacted biological pathways, and independent gene expression datasets were employed to validate the correlation between methylation and gene expression. Our analysis identified robust hypermethylation events, particularly affecting genes involved in extracellular matrix (ECM) organization (P = 2.9E-6, adjusted P = .0017). Prominent methylation changes were mainly observed in promoter regions and first exons of key genes, including ITGA4, FBN1, COL4A1, and COL4A2, with inverse correlations between methylation and gene expression levels. Hierarchical clustering based on CpG island methylation effectively distinguished normal, adenoma, and adenocarcinoma tissues. Across this combined cohort, hypermethylation of ECM-organization genes emerged as a dominant and recurrent epigenetic program along the normal-adenoma-carcinoma sequence. These methylation patterns delineated a characteristic ECM-focused signature that was most pronounced in CRC compared with other malignancies. However, elements of this pattern were also detectable in additional tumor types. As the ECM is pivotal in regulating tumor invasion, immune evasion, and drug resistance, we propose that hypermethylation-associated disruption of ECM function may contribute to CRC progression. Our findings highlight potential biomarkers for early detection and novel therapeutic targets for epigenetic intervention.
Artificial intelligence in gynecologic oncology: A cautionary look in the Indian context.
Kumari S, Chandra R, Tiwari A
Semin Oncol · 2026 Apr · PMID 41494506 · Publisher ↗
Artificial intelligence (AI) is making remarkable strides in the field of oncology. The potential is humongous, but the perils are understated. From the perspective of gynecologic oncologists from India, we urge everyone...
Artificial intelligence (AI) is making remarkable strides in the field of oncology. The potential is humongous, but the perils are understated. From the perspective of gynecologic oncologists from India, we urge everyone to take a cautionary look at the rapid AI evolution in oncology.
Immuno-oncology approaches to overcome T cell exhaustion in melanoma.
El-Sehrawy AAMA, Alshahrani MY, Fedwi MM … +7 more , Ganesan S, Al-Khafaji ZA, Arora V, Pal A, Nayak PP, Islomov S, Hsu CY
Semin Oncol · 2026 Feb · PMID 41455351 · Publisher ↗
Melanoma, a highly aggressive type of skin cancer, has undergone incredible developments in immunotherapy, particularly in modulating T-cell immunity. T cells are essential components of the antitumor immune response and...
Melanoma, a highly aggressive type of skin cancer, has undergone incredible developments in immunotherapy, particularly in modulating T-cell immunity. T cells are essential components of the antitumor immune response and can undoubtedly influence the effectiveness of melanoma treatment. This review will evaluate the roles of the different T cell subsets (CD8, CD4, and Tregs) in melanoma immunity. CD8 T cells are important effectors, as they primarily recognize and kill tumor cells. However, CD8+ T cells are often dysfunctional due to exhaustion driven by chronic antigen exposure and dysfunctional immune checkpoint pathways, specifically PD-1 and CTLA-4. On the other hand, CD4 T cells, also known as T helper cells, play a crucial role in coordinating both pro- and antitumor immune responses. In contrast to T cells, Tregs, which are often present in the tumor microenvironment, lead to immune suppression through their activity, limiting T cell activity. This review will also examine the mechanisms of T-cell exhaustion, metabolic reprogramming within the tumor microenvironment (TME) of T-cell subsets, and the role of immune checkpoint pathways, such as CTLA-4 and PD-1, in T-cell immunity. Adoptive cell therapies (ACT), specifically Tumor-Infiltrating Lymphocyte (TIL) therapy and Chimeric Antigen Receptor (CAR) T-cell therapy, have shown the ability to rejuvenate T-cells to enhance clinical outcomes. However, several resistance mechanisms and the suppressive TME presents difficulties. Future efforts will focus on combination therapies, metabolic interventions, and novel engineering techniques to overcome barriers to T-cell function exhaustion and T-cell persistence. Evaluating biomarkers associated with early prediction for therapeutic benefit and associated toxicity is important for personalizing a particular treatment. Ultimately, this review highlights the potential of targeting T-cell exhaustion to enhance the effectiveness of T-cell-based therapies in improving outcomes for melanoma patients.
Submicron silica particles drives prostate cancer aggressiveness via lipid-metabolic reprogramming.
Su P, Xu Q, Wang Y … +9 more , Xie W, Lin J, Zhuo Y, Ye J, Lu J, Han Z, Zou F, Dai Q, Zhong W
Semin Oncol · 2026 Feb · PMID 41337831 · Publisher ↗
Micron-sized (1 µm - 100 µm) and submicron-sized (100 nm-1 µm) silica particles are prevalent in both natural environments and areas influenced by human activities. Their environmental forms, origins, and pathways of hum...
Micron-sized (1 µm - 100 µm) and submicron-sized (100 nm-1 µm) silica particles are prevalent in both natural environments and areas influenced by human activities. Their environmental forms, origins, and pathways of human exposure differ markedly from those of nanoscale silica. Empirical studies have demonstrated that silica can induce cellular oxidative stress and mitochondrial dysfunction, as well as inhibit the activity of key enzymes in the tricarboxylic acid (TCA) cycle, such as isocitrate dehydrogenase. This inhibition can promote tumor cell proliferation and invasion. Furthermore, silica may activate the HIF-1α/mTOR signaling axis, leading to the upregulation of glucose transporter GLUT1 and lactate dehydrogenase (LDHA), thereby enhancing glycolytic metabolic flux. Concurrently, it may inhibit fatty acid β-oxidation, resulting in abnormal lipid accumulation and the promotion of pro-inflammatory mediator release. In summary, the accumulation of submicron silica within the bodies of cancer patients has the potential to induce metabolic disorders. Such metabolic reprogramming may influence the progression of prostate cancer (PCa) and adversely impact postoperative quality of life. In this study, we demonstrated that prolonged exposure of the lungs to submicron silica particles can induce alterations in lipid metabolism in PCa and significantly enhance the proliferation and invasive capacity of PCa cells. Consequently, elucidating the mechanisms underlying silica-induced metabolic imbalance holds substantial clinical significance for enhancing the prognosis of patients with tumors related to exposure.
Targeting TRP channels in oral cancer: Mechanistic potential and therapeutic promise.
Renu K, Veeraraghavan VP, Madhyastha H
Semin Oncol · 2026 Feb · PMID 41330208 · Publisher ↗
Oral cavity cancer remains a major clinical challenge due to its aggressive nature, rapid lymphatic spread, and limited therapeutic options. Despite advancements in diagnosis and treatment, patient prognosis continues to...
Oral cavity cancer remains a major clinical challenge due to its aggressive nature, rapid lymphatic spread, and limited therapeutic options. Despite advancements in diagnosis and treatment, patient prognosis continues to be poor, highlighting the urgent need for novel molecular targets. This review systematically examines the critical role of calcium (Ca²⁺) ion channels, particularly transient receptor potential (TRP) channels, in the initiation and progression of oral cancer. Comprehensive searches were conducted in Scopus, Embase, Web of Science, and Google Scholar databases up to January 2025. The focus centers on TRPA1, TRPV1-4, TRPM2, TRPM6, and TRPM8 channels, emphasizing their dysregulated expression, altered functionality, and downstream signaling in oral squamous cell carcinoma (OSCC). Emerging evidence demonstrates that aberrant TRP channel activity contributes to enhanced cell proliferation, migration, invasion, and survival, thereby promoting oral carcinogenesis. Additionally, the review explores the interplay between TRP-mediated calcium signaling and oncogenic pathways such as PI3K/AKT and MAPK, elucidating their collective impact on tumor behavior. By integrating insights from molecular biology, pharmacology, and clinical studies, this work underscores the therapeutic potential of targeting TRP channels as a novel approach in oral cancer management. Future research directions include delineating channel-protein interactions and developing selective TRP inhibitors to improve treatment outcomes.
UBE2T promotes papillary thyroid carcinoma progression by activating the JAK/STAT3 pathway via negative regulation of SOCS2.
Zhang L, Li C, Zhou J … +8 more , Zhang X, Fang H, Cai J, Tong H, Wen J, Zhang H, Shen M, Si Y
Semin Oncol · 2026 Feb · PMID 41330207 · Publisher ↗
Papillary thyroid carcinoma (PTC) exhibits aggressive behaviors such as tumor invasion and lymph node metastasis that critically influence prognosis, yet reliable predictors of invasiveness remain elusive. This study inv...
Papillary thyroid carcinoma (PTC) exhibits aggressive behaviors such as tumor invasion and lymph node metastasis that critically influence prognosis, yet reliable predictors of invasiveness remain elusive. This study investigated the molecular mechanisms through which ubiquitin-conjugating enzyme E2T (UBE2T) drives PTC progression. Bioinformatics analysis of TCGA/GEO datasets and validation with institutional clinical samples revealed UBE2T overexpression correlated with advanced clinicopathological features. Functional experiments demonstrated that UBE2T overexpression enhanced PTC cell invasiveness, while its knockdown suppressed malignant behaviors. Mechanistically, co-immunoprecipitation identified cytokine signaling suppressor 2 (SOCS2) as a key interactor mediating UBE2T's effects on JAK-STAT3 pathway activation. Rescue experiments and immunofluorescence confirmed UBE2T promotes oncogenesis by destabilizing SOCS2, thereby relieving its inhibition of STAT3 phosphorylation. These findings establish UBE2T as a novel regulator of PTC progression through SOCS2/JAK-STAT3 axis manipulation, providing potential therapeutic targets to mitigate metastasis and recurrence in aggressive thyroid carcinomas.
The role of circular RNAs in driving cancer advancement in low-oxygen conditions.
Owida HA, Saleh RO, Mohammad SI … +7 more , Vasudevan A, R R, Kashyap A, Nanda A, Ray S, Hussein A, Yasin HA
Semin Oncol · 2026 Feb · PMID 41317529 · Publisher ↗
Oxygen shortage, or hypoxia, is a unifying feature of solid tumors that broadly characterizes cancer biology and therapeutic outcome. In expanding tumors, cells adapt to low oxygen tensions by undergoing extensive metabo...
Oxygen shortage, or hypoxia, is a unifying feature of solid tumors that broadly characterizes cancer biology and therapeutic outcome. In expanding tumors, cells adapt to low oxygen tensions by undergoing extensive metabolic reorganization, which is mainly orchestrated by hypoxia-inducible factor-1α (HIF-1α). The adaptive response initiates epithelial-mesenchymal transition (EMT), promotes metastatic dissemination, and facilitates the formation of cancer stem-like states that drive therapy resistance. Apart from such cellular reorganization, hypoxia also affects circular RNA (circRNA) biogenesis and function, a unique category of non-coding RNAs. CircRNAs are deposited into the tumor microenvironment to function as gene-expression regulators and signaling cascade modulators that are critical for survival, invasion, and drug resistance. Their unique hypoxia-associated expression patterns render them the first choice for diagnosis and prognosis. In this work, we examine the intricate relationship between circRNAs and hypoxia as well as associated molecular mechanisms. We also emphasize their role as ceRNAs, about microRNA binding and RNA-binding proteins, and their oncogenic role. Finally, we underscore the potential of targeting hypoxia-responsive circRNAs as novel therapeutic strategies for cancer.
Genome editing of immune checkpoints: CRISPR-mediated PD-1 inhibition in cancer.
Mohammad SI, Kareem AK, Vasudevan A … +7 more , Rekha MM, Jabir MS, Nayak P, AlKhafaje Z, Arora V, Kadhum W, Chennakesavulu K
Semin Oncol · 2026 Feb · PMID 41313840 · Publisher ↗
The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is a primary mechanism by which tumors evade immune surveillance, limiting the efficacy of cytotoxic T lymphocytes (CTLs) and...
The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is a primary mechanism by which tumors evade immune surveillance, limiting the efficacy of cytotoxic T lymphocytes (CTLs) and tumor-infiltrating lymphocytes (TILs). Although immune checkpoint blockade therapies have revolutionized cancer treatment, their efficacy is restricted by acquired resistance, T-cell exhaustion, and tumor heterogeneity. The advent of CRISPR-Cas9 genome editing provides a precise and versatile approach to disrupt PD-1 or PD-L1, directly enhancing anti-tumor immune responses. Preclinical studies demonstrate that ex vivo PD-1 knockout in primary human T cells or TILs enhances proliferation, cytokine production, and cytotoxicity, resulting in improved tumor clearance in xenograft and humanized mouse models. In chimeric antigen receptor (CAR) T cell therapy, CRISPR-mediated disruption of PD-1 improves effector function, persistence, and resistance to exhaustion, with universal and allogeneic CAR-T platforms benefiting from multiplex genome editing. Direct PD-L1 knockout in tumor cells, often facilitated via nanoparticle- or biomaterial-assisted delivery, reshapes the immunosuppressive tumor microenvironment, promotes T cell infiltration, and enhances the efficacy of adoptive cellular therapy. Combination approaches integrating PD-1 editing with viral antigen targeting, long noncoding RNA (lncRNA) modulation, or conventional checkpoint blockade demonstrate synergistic anti-tumor effects. Clinically, early-phase trials in non-small cell lung cancer, mesothelin-positive solid tumors, and hematological malignancies establish the feasibility, safety, and preliminary efficacy of PD-1-deficient T cells. Despite these promising outcomes, challenges such as off-target effects, delivery efficiency, immunogenicity, long-term persistence, and regulatory considerations remain. This review aims to comprehensively evaluate preclinical and clinical studies investigating CRISPR-mediated PD-1/PD-L1 inhibition across various cancers, summarize mechanistic insights, and highlight translational opportunities and challenges for clinical implementation.
Comparative efficacy of osimertinib with and without radiation therapy in EGFR-mutated nonsmall cell lung cancer with brain metastases.
Aibani R, Collins J, Borna AK … +1 more , Kamran A
Semin Oncol · 2026 Feb · PMID 41285061 · Publisher ↗
Brain metastases are common in patients with EGFR-mutant nonsmall cell lung cancer (NSCLC), yet optimal management remains under investigation. Osimertinib has demonstrated central nervous system (CNS) activity, but the...
Brain metastases are common in patients with EGFR-mutant nonsmall cell lung cancer (NSCLC), yet optimal management remains under investigation. Osimertinib has demonstrated central nervous system (CNS) activity, but the added benefit of combining it with upfront local therapy is unclear. This study evaluated the comparative efficacy of osimertinib alone versus in combination with radiation therapy (RT) or stereotactic radiosurgery (SRS) in patients with EGFR-mutant NSCLC and brain metastases. We conducted a retrospective cohort study using the TriNetX Research Network, identifying adult patients diagnosed between 2010 and 2024 with EGFR-mutant NSCLC and brain metastases who received osimertinib. Patients were grouped into those who received RT or SRS within 6 months of starting osimertinib (cohort 1) and those who received osimertinib alone (cohort 2). Propensity score matching (1:1) was used to balance baseline characteristics. The primary outcome was 3-year survival; secondary outcomes included CNS complications, healthcare utilization, and second-line therapy initiation. Among 743 eligible patients, 217 in each cohort were matched. Three-year survival was significantly higher in cohort 1 (43% v 29%; HR 0.67, P = .003). Median survival was 25 months v 16 months, respectively. CNS complication rates were not significantly different overall, though sensitivity analysis excluding prior CNS history showed increased complications with osimertinib alone (HR 2.0, P = .007). SRS was independently associated with reduced mortality (HR 0.49, P = .003). Upfront local therapy with osimertinib may improve survival in EGFR-mutant NSCLC with brain metastases, though careful patient selection is warranted.
Nanoparticle-based approaches for doxorubicin delivery in hepatocellular carcinoma: Current strategies and emerging innovations.
Alkhathami AG, Ahmed AT, Hussn A … +7 more , RenukaJyothi S, Panigrahi R, Al-Hetty HRAK, Negi H, Jassal P, Hammady FJ, Salih SA
Semin Oncol · 2026 Feb · PMID 41273988 · Publisher ↗
Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, but HCC treatment with the chemotherapeutic doxorubicin is limited because of acquired drug resistance. In this review, w...
Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, but HCC treatment with the chemotherapeutic doxorubicin is limited because of acquired drug resistance. In this review, we examined current knowledge on the specific molecular mechanisms of doxorubicin resistance in HCC, including overexpression of drug efflux (ABC family) transporters, aberrations of the drug target topoisomerase IIα (TOP2A), impairments in apoptosis (p53, FOXO3, Bcl-2 family members), oncogenic activation of pro-survival signaling pathways (NF-κB, PI3K/Akt, and MAPKs), instances of tumor heterogeneity with sirtuins, and cancer stem cells. Additionally, we investigate the role of non-coding RNAs, particularly microRNAs and long non-coding RNAs, in modulating sensitivity to and resistance to doxorubicin in HCC. In conclusion, nanomedicine will become crucial in overcoming the limitations of significant doxorubicin resistance in HCC, utilizing advanced mechanisms to modulate treatment with doxorubicin in this context. This review details various nanotechnology-based approaches to the delivery of doxorubicin, including passive targeting using the enhanced permeability and retention (EPR) effect, active targeting with specific ligands, and stimulus-responsive drug release in the tumor microenvironment (e.g., pH, redox potential). We focus on preclinical studies that utilized a variety of nanoparticle formulations for palliative care to patients with HCC, have investigated the use of liposomes, polymeric nanoparticles (e.g., PCL, chitosan), metallic particles (e.g., gold, silver, iron oxide), dendrimers, and metal-organic frameworks (MOFs), which have been loaded with doxorubicin or combined with other agents (e.g., cantharidin, berberine, isoginkgetin, ginger extract). The nanoparticle formulations enhanced drug delivery, increased drug accumulation per cell, reduced systemic toxicity, and overcame drug resistance mechanisms in HCC models.
Colchicine as an anti-inflammatory agent improving cancer prognosis: A therapeutic repurposing perspective.
Matza Porges S, Shamriz O, Ben-Sasson SZ
Semin Oncol · 2026 Feb · PMID 41273987 · Publisher ↗
In this Perspective, we highlight colchicine, a centuries-old, widely available anti-inflammatory drug, as a promising therapeutic candidate in oncology. We synthesize evidence demonstrating its ability to target central...
In this Perspective, we highlight colchicine, a centuries-old, widely available anti-inflammatory drug, as a promising therapeutic candidate in oncology. We synthesize evidence demonstrating its ability to target central pathways of cancer biology, including chronic inflammation, angiogenesis, cytoskeletal remodeling, and autophagy, while also mitigating treatment-related comorbidities such as cardiovascular disease.
Artificial intelligence-driven intelligent nanocarriers for cancer theranostics: A paradigm shift with focus on brain tumors.
Pourmadadi M, Shabestari SM, Abdouss H … +3 more , Rahdar A, Fathi-Karkan S, Pandey S
Semin Oncol · 2025 Dec · PMID 41218468 · Publisher ↗
Artificial intelligence (AI) and nanotechnology are revolutionizing brain cancer theranostics by enhancing drug delivery and diagnostic accuracy. This review examines AI-enhanced engineering strategies for developing int...
Artificial intelligence (AI) and nanotechnology are revolutionizing brain cancer theranostics by enhancing drug delivery and diagnostic accuracy. This review examines AI-enhanced engineering strategies for developing intelligent nanocarriers that target glioblastoma and other metastatic central nervous system malignancies. AI encompasses several computational methods, including machine learning (ML) and its subset deep learning (DL). Here, ML algorithms learn design rules for nanocarriers, and DL networks intricate pattern recognition for tumor segmentation and adaptive release. These approaches enable stimuli-responsive nanocarriers to react to tumor microenvironmental signals (eg, pH, enzyme activity) and external stimuli (eg, ultrasound), optimizing targeted medication release while minimizing off-target effects. Magnetic resonance imaging (MRI) and positron emission tomography (PET), in conjunction with AI, enhance tumor detection and segmentation, while the integration of multiomics data facilitates tailored treatment planning. Advanced technologies encompass transferrin-functionalized nanoparticles for traversing the blood-brain barrier (BBB) and dual-stimuli-responsive drug delivery systems. Notwithstanding general progress, apprehensions surrounding batch variability and industrial scalability persist. This review also addresses ethical concerns and cost disparities associated with AI-based therapeutics. The primary development target areas are federated learning for data privacy, explainable artificial intelligence (XAI) for regulatory transparency, and quantum ML for molecular-scale optimization. This paper charts the course to patient-specific, scalable neuro-oncology nanomedicine through the convergence of computational modeling, intelligent materials, and advanced imaging modalities. These themes are explored in greater detail in the introduction, where we lay the groundwork for intelligent nanocarriers, their design with the help of AI, and the clinical need for diagnostics-therapeutics convergence in brain cancer.
Corrigendum to "Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment" [Seminars in Oncology Volume 52, Issue 4, 2025, 152376].
Ordóñez C, Zurita S, Ramírez G … +7 more , Cordeiro F, Garcia-Matamoros K, Huaman-Garaicoa F, Orellana-Manzano A, Sandoya-Onofre L, Roca-Pogo J, Carvajal-Aldaz D
Semin Oncol · 2025 Dec · PMID 41203462 · Publisher ↗
Abstract loading — click title to view on PubMed.
Pretreatment eosinophilia as a biomarker for adverse outcomes in non-small cell lung cancer patients receiving immune checkpoint inhibitors: A systematic review and meta-analysis.
Ganatra N, Thompson J, Desai R … +4 more , Doshi J, Jain P, Pasnoor DS, Jain A
Semin Oncol · 2025 Dec · PMID 41187482 · Publisher ↗
In recent years, immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC), yet treatment response and adverse events vary widely among patients. In response, th...
In recent years, immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC), yet treatment response and adverse events vary widely among patients. In response, the identification of reliable pretreatment biomarkers has become a major goal for many clinicians to enhance prognostication and personalized care. As such, this systematic review and meta-analysis aimed to evaluate whether pretreatment eosinophilia is associated with adverse clinical outcomes in NSCLC patients receiving ICI therapy. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through February 2025. Eligible studies included observational designs reporting associations between baseline eosinophil levels and overall survival, progression-free survival, or immune-related adverse events (irAEs) in ICI-treated NSCLC patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models for both unadjusted and adjusted data. Eleven studies met inclusion criteria. Pretreatment eosinophilia was associated with a nonsignificant reduction in overall survival based on both unadjusted analyses (OR: 0.79, 95% CI: 0.42-1.51 and OR: 0.74, 95% CI: 0.53-1.03, respectively). Similarly, a nonsignificant reduction in progression-free survival was found in unadjusted models (OR: 0.78, 95% CI: 0.54-1.13), whereas adjusted data revealed a significant negative association (OR: 0.68, 95% CI: 0.58-0.80). In contrast, eosinophilia was significantly associated with increased odds of irAEs in both unadjusted and adjusted analyses (OR: 3.19, 95% CI: 2.11-4.83 and OR: 3.35, 95% CI: 2.25-5.02, respectively). These findings indicate that pretreatment eosinophilia may serve as a useful prognostic biomarker indicating increased susceptibility to irAEs and potentially poorer survival outcomes in ICI-treated NSCLC patients.
CAR-T cell therapy: A therapeutic strategy for cancer treatment.
Sharif S, Sharma U, Yadav AK
Semin Oncol · 2025 Dec · PMID 41187481 · Publisher ↗
In the twenty-first century, chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy by offering novel approaches and life-saving treatments for illnesses that were previously incurable. This...
In the twenty-first century, chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy by offering novel approaches and life-saving treatments for illnesses that were previously incurable. This method is currently being used in clinical trials for solid tumors like prostate cancer and glioblastoma, as well as viral and autoimmune illnesses. It has demonstrated impressive efficacy in treating a variety of hematological malignancies. Harvesting a patient's T cells, genetically modifying them using viral vectors to express CARs that target specific antigens, and then reintroducing the altered cells into the patient is the process of CAR-T cell therapy. These CAR-T cells detect and destroy target cells specifically, regardless of the presence of the major histocompatibility complex (MHC) antigen. The major turning points in the development of CAR-T cells, from their creation to their use in medicine, are highlighted in this overview. It describes how CAR-T cells were developed historically, highlights the significant advancements that have made them a ground-breaking treatment, and talks about the obstacles that still need to be overcome, such as the high cost of production, restricted availability, and toxicity problems like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The review also looks at the field's future developments with the goals of increasing therapeutic uses, minimizing toxicity, and maximizing efficacy. With safer and more efficient CAR T cell therapies being developed, we are optimistic that a larger group of cancer patients may soon benefit from this innovative treatment.
Machine learning-based integration develops a lactate metabolism related gene signature for improving outcomes in pancreatic ductal adenocarcinoma.
Ge WL, Hou CQ, Zong QQ … +3 more , Li DR, Peng YP, Li Q
Semin Oncol · 2026 Feb · PMID 41161133 · Publisher ↗
OBJECTIVES: Given its high global mortality rate, pancreatic ductal adenocarcinoma (PDAC) remains a significant area of investigation. However, a robust gene signature linked to lactate metabolism for PDAC patients has n...
OBJECTIVES: Given its high global mortality rate, pancreatic ductal adenocarcinoma (PDAC) remains a significant area of investigation. However, a robust gene signature linked to lactate metabolism for PDAC patients has not yet been established. Our objective was therefore to construct a novel lactate metabolism related gene signature (LMRGS) capable of predicting patient outcomes and informing therapeutic decisions. METHODS: Genes associated with lactate metabolism were sourced from the Molecular Signatures Database (MsigDB). The LMRGS was constructed using distinct algorithmic combinations and its performance was subsequently verified in 8 separate patient cohorts. Multiomics analyses were employed to evaluate the signature's impact on biological functions and to investigate its relationship with the immune microenvironment. EdU, colony formation and wound-healing assays were used to demonstrate the effects of lactate on pancreatic cancer cells. RESULTS: An artificial intelligence framework enabled the creation of an LMRGS that serves as an independent prognostic predictor for individuals with PDAC. This signature demonstrated considerable accuracy in forecasting overall survival. When patients were stratified into high- and low-risk groups, the high-risk group showed reduced immune cell infiltration and a poorer response to immunotherapy. Further investigation confirmed a strong correlation between the LMRGS and the immune milieu in PDAC. In vitro experiments demonstrated that lactate promotes the proliferation and migration of pancreatic cancer cells. CONCLUSION: We have formulated a new LMRGS for PDAC which holds potential for informing personalized treatment plans. Interventions aimed at the lactate metabolic pathway could represent a promising strategy to boost therapeutic effectiveness and extend survival for patients diagnosed with this disease.
The nervous system in prostate cancer: A basic science and clinical perspective.
Sigorski D, Kasprzyk-Pawelec A, Michalak M … +7 more , Sosnowski R, Hryciuk MM, Sejda A, Gulczyński J, Kitlinska J, Nawrocki S, Iżycka-Świeszewska E
Semin Oncol · 2026 Feb · PMID 41138516 · Publisher ↗
Prostate cancer (PCa) constitutes an important health challenge worldwide. The nervous system, in a complex and multimodal manner, regulates prostate physiology and PCa development and affects the course of the disease....
Prostate cancer (PCa) constitutes an important health challenge worldwide. The nervous system, in a complex and multimodal manner, regulates prostate physiology and PCa development and affects the course of the disease. The phenomena of axonogenesis and neurogenesis, first described in PCa, were a breakthrough discovery that changed our understanding of cancer-nerve crosstalk. Different nerve types within the cancer stroma and tumor surroundings create complex interactions between the cancer microenvironment elements based on neurotransmission, affecting the hallmarks of cancer. The most common form of PCa and nerve interaction is the perineural invasion (PNI), which recently has been suggested as a driver of metastases. Additionally, many preclinical discoveries depict the molecular mechanisms of altered nerve activity, showing the pivotal role of sympathetic and parasympathetic signaling systems in localized and advanced PCa, axon-guidance molecules and neurotrophin. The neuroendocrine switch in advanced PCa is one of reasons of lethal, castration-resistant phase of the disease. Knowledge about the infiltration status of the periprostatic nerves present in radiological imaging is important for urologists in planning the treatment. Although some studies suggest that PNI and nerve density may be prognostic factors in PCa, it is necessary to evaluate these indicators better and apply them to practice. The neural-based therapeutic application in PCa is limited currently. Some studies showed that β blockers reduce PCa-specific mortality and neuroendocrine differentiation potential. This review provides a comprehensive, up-to date synthesis of PCa neurobiology, uniquely integrating both preclinial and clinical perspectives.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe