Seminars In Oncology[JOURNAL]
Sun
200 papers
A systematic scoping review of cancer-related anemia treatment: Comparative trial outcomes, current guidelines, and future perspectives.
Elkhalifa DH, Lub-de Hooge MN, Jansman FGA
Semin Oncol · 2026 Jun · PMID 42385497 · Publisher ↗
INTRODUCTION: Cancer-related anemia (CRA) adversely affects quality of life and clinical outcomes. Despite extensive research, uncertainty remains regarding the optimal use of erythropoiesis-stimulating agents (ESAs), ir...
INTRODUCTION: Cancer-related anemia (CRA) adversely affects quality of life and clinical outcomes. Despite extensive research, uncertainty remains regarding the optimal use of erythropoiesis-stimulating agents (ESAs), iron, and transfusions. This scoping review synthesizes efficacy and safety evidence and compares international management guidelines. METHODS: A systematic search of PubMed and Embase identified English-language studies on CRA published from 2000 up to November 30, 2024. Randomized controlled trials were reviewed to assess treatment efficacy and safety, and international guidelines were analyzed to compare management recommendations. RESULTS: Fifty-six randomized controlled trials and 10 international guidelines were included. ESAs and iron supplementation were effective in improving hemoglobin concentration and reducing transfusion requirements, particularly in context-dependent settings. Combination therapy with ESAs and iron consistently demonstrated superior hematologic responses compared with ESA monotherapy without additional safety concerns. Both conventional and newer intravenous (IV) and oral iron formulations showed benefit across different clinical contexts, with faster responses generally favoring IV iron in some settings, while emerging evidence supports oral iron as a viable alternative in absolute iron deficiency. Emerging therapies, including sotatercept and selected adjunctive approaches, showed preliminary signals of efficacy in limited studies, warranting further investigation. Guidelines generally restrict ESAs to chemotherapy-induced anemia or high-risk patients. For iron therapy, discrepancies exist regarding indications and administration route; most guidelines prioritize IV over oral iron for both functional iron deficiency and absolute iron deficiency. Significant regional gaps in guideline availability were identified, particularly in Africa, South America, Asia-Pacific, and the Middle East. CONCLUSION: CRA management relies on ESAs, iron supplementation, and transfusions, but guideline heterogeneity and regional discrepancies necessitate harmonization and individualized approaches. Updated, globally representative recommendations and further research in under-studied populations are essential.
Steroid-induced tumor lysis syndrome in solid tumors: A case report and review of the literature.
Conard R, Trivedi C, Page W
Semin Oncol · 2026 Jun · PMID 42335755 · Publisher ↗
Tumor lysis syndrome (TLS) arises from the uncontrolled release of intracellular contents into the bloodstream. Generally associated with hematologic malignancies, TLS has also been reported in aggressive solid cancers....
Tumor lysis syndrome (TLS) arises from the uncontrolled release of intracellular contents into the bloodstream. Generally associated with hematologic malignancies, TLS has also been reported in aggressive solid cancers. Corticosteroids are known triggers of cell lysis in leukemias and lymphomas, but less evidence exists to suggest steroids cause TLS in solid malignancies. We present a case of a 43-year-old smoker with dyspnea, cough, and chest pain. Endobronchial biopsy confirmed the diagnosis of extensive-stage small-cell carcinoma. He remained intubated due to airway edema and was started on dexamethasone. Prior to steroid administration, his blood chemistry values were within reference ranges. The following day, he met both laboratory and clinical Cairo-Bishop criteria for TLS. Despite IV hydration and rasburicase, he worsened and was transitioned to comfort care. This case suggests one of the clearest associations between steroid administration and TLS in a solid tumor. We systematically explored PubMed for cases of TLS in solid tumors and evaluated these for steroid use prior to diagnosis. Of the 252 included articles, 20 described corticosteroid use before the onset of TLS, with only 10 explicitly suggesting steroids may have been causative. While rare in solid tumors, TLS should be considered in any aggressive solid malignancy. A high index of suspicion is essential as early recognition and management of TLS are associated with improved outcomes. We encourage particular attention to be paid after steroids have been administered.
PSMA PET/CT staging in intermediate-risk prostate cancer: Toward risk-adapted implementation.
Petrelli F, Motta F, Bodrato S … +10 more , De Stefani A, Dottorini L, Trevisan F, Bruschieri L, Riboldi V, Esposito A, Mattiello M, Vavassori I, Manfredi A, Seghezzi S
Semin Oncol · 2026 Jun · PMID 42320333 · Publisher ↗
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Angiogenesis and the corresponding antiangiogenic therapy in gastroenteropancreatic neuroendocrine neoplasms.
Li HY, Peng MZ, Tang LH … +4 more , Li JA, Jin Y, Liu L, Wang WQ
Semin Oncol · 2026 May · PMID 42302449 · Publisher ↗
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a well-known group of malignancies characterized by hypervascularization, and much of the focus in this field has been on angiogenesis. Rather than simply an...
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a well-known group of malignancies characterized by hypervascularization, and much of the focus in this field has been on angiogenesis. Rather than simply an increase in microvessel density, angiogenesis of GEP-NENs is a far more sophisticated process regulated by angiogenic factors, genes, and cells. These angiogenesis-related factors are not only involved in tumorigenesis and progression but also serve as biomarkers with prognostic values and targets for antiangiogenic therapy. Extensive research has been conducted on the role of various angiogenesis-related factors in angiogenesis, their prognostic values, and antiangiogenic therapy has become a critical part of the treatment of GEP-NENs. However, the occurrence of drug resistance and unsatisfactory prognosis reminds us that our understanding of angiogenesis of GEP-NENs is insufficient, and we are in urgent need to optimize existing antiangiogenic therapies. This review focuses on angiogenesis-related factors, their roles in angiogenesis, as well as their values in predicting the prognosis of patients, and introduces the corresponding angiogenic therapies. By summarizing current research findings, we aim to shed light on the mechanism of angiogenesis of GEP-NENs and to elucidate prospects for more accurate prediction of prognosis and individualized antiangiogenic therapies.
Post-translational regulation of steroidogenesis and its clinical relevance in hormone responsive cancers.
Sankar R, Venkatraman G
Semin Oncol · 2026 May · PMID 42275676 · Publisher ↗
Hormone-related cancers represent a significant global health concern, contributing to substantial mortality rates worldwide. The intricate interplay of steroidogenesis, the biochemical pathway governing hormone synthesi...
Hormone-related cancers represent a significant global health concern, contributing to substantial mortality rates worldwide. The intricate interplay of steroidogenesis, the biochemical pathway governing hormone synthesis, plays a pivotal role in the development and progression of these malignancies. Dysregulation of key steroidogenic enzymes can disrupt physiological and biological processes, thereby driving malignant transformation. Post-translational modifications of these enzymes play an important role in modulating their activity, stability, and subcellular localization, thereby potentially influencing cancer progression. This study provides a comprehensive analysis of the functionality and regulatory mechanisms of four key steroidogenic enzymes, Desmolase, 17α-hydroxylase, 3β-HSD (3β-hydroxysteroid dehydrogenase), and 17β-HSD (17β-hydroxysteroid dehydrogenase), along with a transporter protein (steroidogenic acute regulatory protein [StAR]). We present an integrated overview of their expression patterns, domain architectures, reported post-translational modification sites, and the kinases involved. By elucidating these molecular details, our work highlights novel avenues for targeted therapy in hormone-related cancer research.
Physics-informed machine learning for tumor microenvironment-responsive nanomedicine: Recent updates.
Hasannia M, Abounoori A, Abounoori M … +4 more , Shirzad M, Rahdar A, Fathi-Karkan S, Romanholo Ferreira LF
Semin Oncol · 2026 Apr · PMID 42214280 · Publisher ↗
Physics-informed machine learning (PIML) is rapidly emerging as a transformative paradigm for designing tumor microenvironment (TME)-responsive nanomedicines. While existing reviews have surveyed PIML in broader biomedic...
Physics-informed machine learning (PIML) is rapidly emerging as a transformative paradigm for designing tumor microenvironment (TME)-responsive nanomedicines. While existing reviews have surveyed PIML in broader biomedical contexts, this work provides a focused, critical synthesis specifically at the intersection of PIML, multiscale TME biophysics, and clinically actionable nanomedicine design. We argue that the unique value of PIML lies not merely in combining physics with data, but in its capacity to resolve the "personalization paradox" in oncology: the tension between the need for patient-specific models and the scarcity of patient-specific data. By embedding governing physical laws-such as Darcy's flow, reaction-diffusion kinetics, and Navier-Stokes equations-as soft constraints, PIML models can generate physically plausible, patient-tailored predictions even with sparse clinical inputs. This review uniquely articulates a translational roadmap that systematically links fundamental PIML methodologies to concrete nanomedicine optimization tasks: predicting nanoparticle transport in heterogeneous TMEs, designing stimulus-responsive nanocarriers, and integrating multi-omics/imaging for personalized therapy. We further introduce a novel comparative framework evaluating PIML against purely physics-based and purely data-driven approaches, highlighting its superior data efficiency and interpretability for TME applications. However, significant challenges remain, including data standardization, computational scalability, and regulatory adaptation. Looking forward, we identify under-explored yet high-impact frontiers, such as quantum-informed PIML for molecular-scale nanocarrier design, real-time adaptive nanomedicine guided by patient digital twins, and the ethical-regulatory frameworks needed for clinical deployment. By synthesizing cross-disciplinary insights and proposing a clear path from bench to bedside, this review aims to not only summarize the state-of-the-art but also to catalyze the next generation of intelligent, patient-centric cancer nanotherapeutics.
Stoma-free precision sphincter-preserving surgery with J-pouch for metastatic low rectal neuroendocrine tumor.
Lai L, Li K, Yang W … +2 more , Zhang X, Liu Z
Semin Oncol · 2026 May · PMID 42202603 · Publisher ↗
R0 resection and maximal preservation of anal function without a permanent stoma remains challenging in patients with a rectal neuroendocrine neoplasm (R-NEN) within 5 cm of the anal verge and lymph node metastasis in th...
R0 resection and maximal preservation of anal function without a permanent stoma remains challenging in patients with a rectal neuroendocrine neoplasm (R-NEN) within 5 cm of the anal verge and lymph node metastasis in the iliac vascular region. A 22-year-old man presented with a 1-year history of paroxysmal palpitations and cold sweats. Colonoscopy revealed a 2-cm mass with well-defined margins located 5 cm from the anal verge. Biopsy revealed a neuroendocrine tumor. Endoscopic submucosal dissection and pathology revealed a G2 R-NEN with negative margins but vascular invasion. Enhanced MRI and whole-body PET/CT identified metastases in the left iliac and right common iliac vascular regions with presacral lymph node involvement. The patient underwent precision functional sphincter-preserving surgery combined with colonic J-pouch anal anastomosis without a stoma. The patient started oral short-peptide enteral nutrition on postoperative day (POD)3 and advanced to a liquid diet on POD8 and a semi-liquid diet on POD10. He was discharged on POD12, with no anastomotic leakage observed within 30 days. Histopathology confirmed stage T1bN1M0 disease. At the 7-month follow-up, the patient reported satisfactory anal, urinary, and sexual function and had maximal global health and quality of life scores. The favorable outcomes in this young case of G2 R-NEN suggests that precision functional sphincter-preserving surgery integrated with a colonic J-pouch may be a clinical reference for achieving oncological radicality while optimizing physiological outcomes. This strategy offers an alternative to traditional radical surgery for young patients and those with high functional demands. However, its safety, functional durability, and oncological efficacy require confirmation in larger, prospective multicenter studies with longer follow‑up.
FDA approval of avutometinib + defactinib (Avmapki Fakzynja) for KRAS-mutant LGSOC: A precision oncology milestone.
Hussain JM, Khan R, Fazal A … +1 more , Kanwal N
Semin Oncol · 2026 May · PMID 42176595 · Publisher ↗
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Evaluating the ability of generative AI to standardize TNM staging data in lung cancer.
Altuhaifa FA, Pereira AP, Tuhaifa MAA … +2 more , Alshaikhahmed H, Tuhaifa DA
Semin Oncol · 2026 Jun · PMID 42155548 · Publisher ↗
This study evaluates the ability of generative artificial intelligence (AI) models to standardize tumor-node-metastasis (TNM) staging data in lung cancer. It assesses how well two large language models, ChatGPT and Gemin...
This study evaluates the ability of generative artificial intelligence (AI) models to standardize tumor-node-metastasis (TNM) staging data in lung cancer. It assesses how well two large language models, ChatGPT and Gemini, convert information from historical editions of the American Joint Committee on Cancer (AJCC) staging system into the eighth edition. ChatGPT and Gemini were applied to retrospectively standardize TNM staging across multiple AJCC editions using lung cancer data from the Surveillance, Epidemiology, and End Results cancer registry. We used a zero-shot prompting method, employing Python to generate prompts dynamically for each case, and a few-shot variant with examples added to the same inputs. The AI-generated outputs were compared with expert-derived staging to evaluate their accuracy. ChatGPT achieved a micro-accuracy of 52.26% across T, N, M, and stage, slightly outperforming Gemini (50.72%), whereas few-shot prompting improved micro-accuracy to 71.35% and 77.24%, respectively. Both models showed mixed agreement with expert-derived T, N, and M components but often failed to perform the final stage assignment. These results indicate that, although generative AI models may support digital transformation and clinical data standardization, they still face challenges in tasks requiring detailed medical reasoning. Further improvements and validation are needed before relying on generative AI for TNM staging standardization.
Therapeutic potential of natural triterpenoids in pancreatic cancer.
Niu C, Han Y, Zhang J … +1 more , Okolo PI
Semin Oncol · 2026 Apr · PMID 42119258 · Publisher ↗
Pancreatic cancer remains one of the most lethal of malignancies with a 5-year survival rate of approximately 10% in the USA, largely owing to its late diagnosis, intrinsic chemoresistance, and high incidence of metastat...
Pancreatic cancer remains one of the most lethal of malignancies with a 5-year survival rate of approximately 10% in the USA, largely owing to its late diagnosis, intrinsic chemoresistance, and high incidence of metastatic disease. Although gemcitabine-based chemotherapy is the standard treatment for advanced pancreatic cancer, inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment result in conventional cancer treatments having little impact on patient's disease course. Therefore, the development of novel and effective therapies is urgently required. Triterpenoids are naturally occurring secondary metabolites biosynthesized following the isoprene rule of Ruzicka, with a basic nucleus of 30 carbon atoms. Growing evidence from preclinical studies indicates natural triterpenoids as potential anticancer agents against pancreatic cancer. In this review, we synthesize research findings from available preclinical studies that investigated the therapeutic potential of natural triterpenoids on pancreatic cancer, particularly focusing on anticancer mechanisms involving activation of apoptosis, induction of autophagy, regulation of immune responses, inhibition of metastasis, and enhancement of chemosensitivity. We also discuss the key challenges and envisage future research directions in this rapidly evolving field. We conclude that natural triterpenoids are a valuable resource for developing novel therapeutic agents against pancreatic cancer. We also hope that the knowledge gained from this narrative review will be helpful in accelerating the translation of triterpenoid-based therapeutics into clinical practice.
Risk of intensive care unit admission after immune checkpoint inhibitor use in cancer.
Baral MR, Bhandari S, Morgensztern D … +3 more , McEvoy C, Guarin G, Ranganathan P
Semin Oncol · 2026 Apr · PMID 42102588 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause excessive immune activation, leading to severe adverse events, including intensive care unit (ICU) admission. Existing evidence on critica...
Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause excessive immune activation, leading to severe adverse events, including intensive care unit (ICU) admission. Existing evidence on critical illness after ICI use is limited, largely single center, and focused on immune related adverse events. This study evaluates the risk of inpatient and ICU admissions after ICI initiation using two large national databases. We retrospectively analyzed MarketScan Commercial and Multi-state Medicaid Research Databases (2016-2022) to identify adults with solid organ malignancies treated with ICIs and determined if ICU admission was required within 90 days of ICI administration. The primary diagnosis for ICU admission was identified and categorized. Associations between cancer type, ICI type, and ICU admission were analyzed. About 33,040 patients received ICIs during the study period. About 48.9% were male and 51.1% female. Pembrolizumab was the most used (49.3%), followed by nivolumab (31.9%), and ipilimumab (9.4%). Lung cancer was the most common malignancy (40.8%), followed by genitourinary (16%), melanoma (13%), gastrointestinal (12%), and breast (10%). About 22.0% (n = 7,216) of patients were hospitalized, and 8.7% (n = 2,872) required ICU admission. Infection was the most frequent reason for ICU admission, followed by respiratory causes. The odds of being admitted to the ICU were higher with combination ICI (OR = 1.51, P < .001) compared to ICI monotherapy. In conclusion, among patients with solid organ malignancies, nearly 9% required ICU admission within 90 days of ICI initiation, most commonly for infectious causes. These findings highlight the need for heightened vigilance for critical illness in patients treated with ICIs.
Targeting TREM2tumor-associated macrophages reactivates antitumor immunity and improves anti-PD-1 efficacy in gastric cancer.
Xu T, Xue A, Lin C
Semin Oncol · 2026 Jun · PMID 42054952 · Publisher ↗
BACKGROUND: We have demonstrated that CXCL8⁺ monocyte-derived tumor-associated macrophages (TAMs) promote autonomous PD-L1 expression, thereby fostering an immunosuppressive tumor microenvironment. Nevertheless, the func...
BACKGROUND: We have demonstrated that CXCL8⁺ monocyte-derived tumor-associated macrophages (TAMs) promote autonomous PD-L1 expression, thereby fostering an immunosuppressive tumor microenvironment. Nevertheless, the functional contribution of tissue-resident macrophages to immune escape remains largely unexplored. METHODS: The study incorporated four independent cohorts, including two tumor microarray datasets and two groups of transcriptomic profiling data. Associations between TREM2⁺TAMs and clinical outcomes as well as genomic features were evaluated. Additionally, ex vivo culture of fresh tumor tissues was conducted to evaluate the potential therapeutic efficacy of dual blockade targeting PD-1 and TREM2 in gastric cancer. RESULTS: TREM2⁺TAMs level was significantly associated with reduced overall survival in patients with resectable gastric cancer. Notably, a high density of TREM2⁺TAMs correlated with poorer response to immune checkpoint inhibitor. Mechanistically, TREM2⁺TAMs were found to drive CD8⁺T cell exhaustion through dual expression of PD-L1 and Arg1. Blockade of TREM2 sensitized tumors to pembrolizumab and enhanced antitumor immunity, particularly in tumors with high TREM2⁺TAMs infiltration. CONCLUSIONS: TREM2⁺TAMs infiltration served as an independent prognosticator in patients with gastric cancer. TREM2⁺TAMs promoted tumor immune escape through concomitant expression of PD-L1 and Arg1. Dual blockade targeting both PD-1 and TREM2 enhanced antitumor responses in TREM2⁺TAMs tumors, suggesting a promising therapeutic strategy for gastric cancer.
Role of magnolol in gastrointestinal cancers: Recent trends and future perspectives.
Tuli HS, Pal D, Chauhan R … +7 more , Sood A, Mehrotra A, Chauhan A, Bhatia R, Haque S, Sak K, Kaur D
Semin Oncol · 2026 Apr · PMID 42054835 · Publisher ↗
Gastrointestinal cancers represent a major global health burden and are associated with high morbidity and mortality worldwide. Despite advances in conventional therapies, treatment outcomes remain limited due to therapy...
Gastrointestinal cancers represent a major global health burden and are associated with high morbidity and mortality worldwide. Despite advances in conventional therapies, treatment outcomes remain limited due to therapy resistance, toxicity, and poor long-term efficacy, highlighting the need for novel and complementary therapeutic strategies. Magnolol, a biphenolic lignan isolated from Magnolia officinalis, has attracted considerable attention due to its reported anticancer activity in multiple gastrointestinal malignancies. This review systematically summarizes current preclinical evidence on the anticancer effects of magnolol in oral, esophageal, gastric, colorectal, pancreatic, and liver cancers. Available studies demonstrate that magnolol inhibits cancer cell proliferation, migration, invasion, angiogenesis, and epithelial-mesenchymal transition, while inducing cell cycle arrest and apoptosis. These effects are mediated through modulation of key cancer-associated signaling pathways, including PI3K/Akt/NF-κB, MAPK/JNK, ERK, TGF-β/Smad, and caspase-dependent apoptotic pathways. The review further highlights recent insights into the structure-activity relationship of magnolol and its semi-synthetic derivatives, emphasizing how targeted chemical modifications influence anticancer potency and mechanistic specificity. In addition, challenges related to magnolol's poor aqueous solubility, rapid metabolism, and limited bioavailability are discussed, with particular focus on nanotechnology-based delivery systems developed to improve its pharmacokinetic profile and therapeutic performance. This current review provides an integrated overview of magnolol's molecular mechanisms, chemical optimization strategies, and translational limitations in gastrointestinal cancer therapy, and outlines future research directions necessary to support its progression toward clinical application.
Exosomes as emerging biomarkers in breast, lung, and colorectal cancer diagnosis: A comprehensive review.
Yildirim I, Avci CB
Semin Oncol · 2026 Apr · PMID 42054834 · Publisher ↗
Although exosome research has advanced considerably, clinical implementation remains limited. In contrast to previous reviews that catalog numerous biomarkers, this review focuses on translationally ready candidates for...
Although exosome research has advanced considerably, clinical implementation remains limited. In contrast to previous reviews that catalog numerous biomarkers, this review focuses on translationally ready candidates for breast, lung, and colorectal cancers. Exosomal signatures address key diagnostic challenges, such as enabling tissue-free molecular subtyping in breast cancer, distinguishing malignant from benign nodules in lung cancer, and detecting CEA-negative or premalignant adenomas in colorectal cancer. This review critically assesses clinically advanced biomarkers-including miRNAs, lncRNAs, circRNAs, and proteins-and highlights those with validated, high diagnostic performance relative to current standards (e.g., CEA, imaging). Single biomarkers often fail to capture tumor heterogeneity, whereas multi-omic panels integrated with clinical data improve diagnostic accuracy. Exosomal biomarkers should, therefore, be considered adjuncts to standard diagnostics, functioning as triage tools to enhance patient management. The integration of exosomes into clinical workflows holds significant promise for non-invasive, early cancer detection, and personalized medicine.
Pregnancy during pembrolizumab therapy for triple-negative breast cancer with onset of congenital hypothyroidism: Case report, literature review, and caution for clinical practice.
Vagnet A, Ferraj M, Dobi E … +1 more , Valnet Rabier MB
Semin Oncol · 2026 Jun · PMID 41967388 · Publisher ↗
Cancer during pregnancy is rare but increasingly reported due to advanced maternal age and improvements in prenatal diagnostics leading to incidental detection. Immune checkpoint inhibitors (ICIs), such as pembrolizumab...
Cancer during pregnancy is rare but increasingly reported due to advanced maternal age and improvements in prenatal diagnostics leading to incidental detection. Immune checkpoint inhibitors (ICIs), such as pembrolizumab (Keytruda), are now used in oncology, particularly for triple-negative breast cancer (TNBC). As IgG antibodies, ICIs cross the placental barrier and may induce immune-mediated effects in the fetus. We report the first documented case of congenital hypothyroidism following inadvertent in-utero exposure to pembrolizumab. The patient, treated with chemotherapy followed by pembrolizumab for TNBC, was found to be pregnant at 24 weeks of gestation. Pembrolizumab was discontinued, and the pregnancy progressed without complications. On the third day of life, the neonate was diagnosed with congenital hypothyroidism caused by in-utero thyroiditis attributed to pembrolizumab. Levothyroxine treatment was initiated, and at 14 months the infant demonstrated normal psychomotor development under continued thyroid hormone supplementation. Endocrine immune-related adverse events, particularly thyroid disorders, are frequent in adults treated with ICIs, but their fetal impact is rarely described. A review of the literature and a query of the international pharmacovigilance database identified only a limited number of in-utero exposure cases, mainly in melanoma, with neonatal outcomes ranging from uneventful deliveries to immune-related complications. This case highlights the risk of endocrine toxicity in neonates exposed to ICIs during pregnancy and underscores the need for multidisciplinary care, appropriate contraceptive counseling during immunotherapy, and long-term follow-up of exposed children as the use of ICIs continues to expand.
LncRNAs in inflammasome regulation: Orchestrating cancer signaling and chemoresistance.
Mukhlif MY, Mahmood SH, Khalaf AA … +7 more , Sanghvi G, Ballal S, Singh A, Sabarivani A, Mishra S, Mustafa YF, Yasin HA
Semin Oncol · 2026 Jun · PMID 41930801 · Publisher ↗
The intricate interplays of chemotherapy, inflammasomes, and long noncoding RNAs (lncRNAs) form an axis characterizing the immunological microenvironment, cancer genesis, and cancer treatment. LncRNAs profoundly regulate...
The intricate interplays of chemotherapy, inflammasomes, and long noncoding RNAs (lncRNAs) form an axis characterizing the immunological microenvironment, cancer genesis, and cancer treatment. LncRNAs profoundly regulate inflammasomes' activation in the tumor microenvironment by activating initiator inflammasomes or inhibiting inhibitory inflammasomes. This change is required for the immune evasion and proliferation of the tumor. LncRNAs, at the same time, might drive the inflammasome overreactions, which are biased toward anti-apoptotic signals, DNA repair, and increase cell survival pathway drive (ie, NF-κB, PI3K-Akt/mammalian target of rapamycin pathways) to establish chemoresistance. One of the hurdles is the low activity of chemotherapy due to this resistance. The mechanisms of lncRNAs require further elucidation in future research as biomarkers of lncRNA-based personalized therapy and in identifying lncRNAs that may serve as targets for reversing drug resistance. Combining immunotherapy and lncRNA-targeted therapy exhibits remarkable synergistic effects on enhancing anti-tumor immunity and cancer treatment effects.
SUMOylation networks drive glioblastoma stemness, microenvironmental remodeling, and resistance.
Ahmed AY, Ullah MI, Prasad KDV … +7 more , Uthirapathy S, Sanghvi G, Mer RM, Sharma Y, Bhakuni PN, Kariem M, Kadhim AJ
Semin Oncol · 2026 Jun · PMID 41921289 · Publisher ↗
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by poor prognosis, high intratumoral heterogeneity, and pronounced therapy resistance, primarily driven by glioma stem cells (GSCs)....
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by poor prognosis, high intratumoral heterogeneity, and pronounced therapy resistance, primarily driven by glioma stem cells (GSCs). SUMOylation, a reversible post-translational modification, has emerged as a critical regulator of GBM progression and therapeutic response. By modifying transcription factors, SUMOylation enhances oncogenic transcriptional programs, contributing to chemoresistance and retinoid resistance. RNA-binding proteins are also affected, influencing exosomal microRNA sorting, invasion, and vasculogenic mimicry. Additionally, SUMOylation of metabolic and cell cycle regulators supports glycolysis, proliferation, and GSC maintenance, highlighting its role in metabolic rewiring. Dysregulation of tumor suppressors through small ubiquitin-like modifier (SUMO)-mediated mechanisms, such as SENP1-dependent deSUMOylation of HIF-1α and β-catenin, promotes stemness and immune evasion. SUMOylation further intersects with angiogenesis, immune regulation, and epigenetic modifiers, including histone deacetylases and zeste homolog 2, shaping tumor plasticity and therapy resistance. Preclinical studies indicate that pharmacological inhibition of SUMOylation with agents like TAK-981, topotecan, or Paromomycin reduces tumor growth, reverses therapy resistance, and enhances radiosensitivity. Moreover, SUMO-related enzymes, such as UBA2, SENP1, and SUMO2/3, may serve as prognostic biomarkers. Understanding SUMOylation in GBM offers insights into tumor biology and identifies potential therapeutic targets to improve patient outcomes.
Concurrent ischemic stroke, pulmonary embolism, and hemorrhagic brain metastasis in pancreatic ductal adenocarcinoma: A case report.
Dahshan A, Youssef AH, Ali MSES … +2 more , Ayoub AMA, Nasser W
Semin Oncol · 2026 Jun · PMID 41916126 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy frequently complicated by paraneoplastic hypercoagulability, known as Trousseau syndrome. While isolated thromboembolic events such as ischemic st...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy frequently complicated by paraneoplastic hypercoagulability, known as Trousseau syndrome. While isolated thromboembolic events such as ischemic stroke or pulmonary embolism (PE) are well-documented in PDAC, the simultaneous occurrence of arterial stroke, venous thromboembolism, and hemorrhagic brain metastasis is exceedingly rare. We present the case of a middle-aged woman with metastatic PDAC who developed an acute ischemic stroke in the context of PE and hemorrhagic metastasis. There was a management dilemma regarding the best options of treatment and possible complications. This report underscores the protean neurologic and thromboembolic manifestations of Trousseau syndrome and highlights the rare but devastating triad of stroke, PE, and hemorrhagic brain metastasis in PDAC. It also emphasizes the importance of individualized, multidisciplinary management strategies when faced with conflicting risks of thrombosis and hemorrhage in patients with advanced malignancy.
Cancer-associated fibroblasts in bladder cancer: Immunosuppressive mechanisms and therapeutic targeting.
Liu Y, Zhao T, Shi R … +3 more , Xie Y, Li M, Wang Y
Semin Oncol · 2026 Jun · PMID 41895066 · Publisher ↗
Bladder cancer (BCa) still confounds treatment and one of the main reasons why is the nature of the immunosuppressive tumor microenvironment formed by cancer-associated fibroblasts (CAFs). The response rate to immune che...
Bladder cancer (BCa) still confounds treatment and one of the main reasons why is the nature of the immunosuppressive tumor microenvironment formed by cancer-associated fibroblasts (CAFs). The response rate to immune checkpoint inhibitors (ICIs) is still low in CAF-rich BCa, emphasizing the need to develop therapeutically for more therapies aimed directly at CAFs. In the past few years advances has been made with single cell analysis and spatial transcriptomics that reveals a degree of heterogeneity of CAFs and that the CAF subtypes are plastic and occupy distinct regions of the tumor where they govern immune cell behavior, treatment responses and resistant phenotypes. The continued development and use of these cutting edge techniques has really moved the field of tumor biology and precision treatment approaches forward. In this review, we explore our current understanding of the spatial organization of CAF populations in BCa and how they are co-opted to regulate T-cell exclusion and exhaustion, and remodel the stroma. We also integrate new evidence on cytokine signaling networks, matrix related changes, and CAF-driven mechanisms that may weaken the effectiveness of ICIs and chemotherapy. In addition, we outline current strategies that aim to target or reprogram CAFs and highlight promising combination approaches that may help overcome stromal barriers. By linking spatial biology with functional pathways and therapeutic implications, this review provides a clearer framework for understanding CAF mediated immunosuppression in BCa and identifies directions that may support the development of more effective treatments.
Prostate cancer: Evolution of multiparametric MRI PI-RADS v2.1 toward biparametric MRI S-PI-RADS.
Scialpi M, Scalera GB, Scialpi P … +6 more , Evangelisti A, Antogiovanni GN, Comite P, Faralli U, Blasi AD, Martorana E
Semin Oncol · 2026 Apr · PMID 41862307 · Publisher ↗
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