Pub Date : 2026-04-01Epub Date: 2025-12-13DOI: 10.1016/j.seminoncol.2025.152456
Sarita Kumari , Rudrika Chandra , Abhinav Tiwari
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.
{"title":"Artificial intelligence in gynecologic oncology: A cautionary look in the Indian context","authors":"Sarita Kumari , Rudrika Chandra , Abhinav Tiwari","doi":"10.1016/j.seminoncol.2025.152456","DOIUrl":"10.1016/j.seminoncol.2025.152456","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 2","pages":"Article 152456"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-28DOI: 10.1016/j.seminoncol.2025.152428
Wan-Li Ge , Chao-Qun Hou , Qing-Qing Zong , Dan-Rui Li , Yun-Peng Peng , Qiang Li
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.
{"title":"Machine learning-based integration develops a lactate metabolism related gene signature for improving outcomes in pancreatic ductal adenocarcinoma","authors":"Wan-Li Ge , Chao-Qun Hou , Qing-Qing Zong , Dan-Rui Li , Yun-Peng Peng , Qiang Li","doi":"10.1016/j.seminoncol.2025.152428","DOIUrl":"10.1016/j.seminoncol.2025.152428","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152428"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Colchicine as an anti-inflammatory agent improving cancer prognosis: A therapeutic repurposing perspective","authors":"Sigal Matza Porges PhD , Oded Shamriz MD, PhD , Shlomo Z Ben-Sasson PhD","doi":"10.1016/j.seminoncol.2025.152437","DOIUrl":"10.1016/j.seminoncol.2025.152437","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152437"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-30DOI: 10.1016/j.seminoncol.2025.152435
Hamza Abu Owida , Raed Obaid Saleh , Suleiman Ibrahim Mohammad , Asokan Vasudevan , Roopashree R , Aditya Kashyap , Anima Nanda , Subhashree Ray , Ahmed Hussein , Hatif Abdulrazaq Yasin
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.
{"title":"The role of circular RNAs in driving cancer advancement in low-oxygen conditions","authors":"Hamza Abu Owida , Raed Obaid Saleh , Suleiman Ibrahim Mohammad , Asokan Vasudevan , Roopashree R , Aditya Kashyap , Anima Nanda , Subhashree Ray , Ahmed Hussein , Hatif Abdulrazaq Yasin","doi":"10.1016/j.seminoncol.2025.152435","DOIUrl":"10.1016/j.seminoncol.2025.152435","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152435"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-02DOI: 10.1016/j.seminoncol.2025.152436
Rafi Aibani , Jennifer Collins , Amir-Kabirian Borna , Amir Kamran
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.
脑转移在egfr突变的非小细胞肺癌（NSCLC）患者中很常见，但最佳治疗方法仍在研究中。奥西替尼已经显示出中枢神经系统（CNS）的活性，但将其与前期局部治疗联合使用的额外益处尚不清楚。本研究评估了奥西替尼单独与联合放疗（RT）或立体定向放射手术（SRS）治疗egfr突变的非小细胞肺癌和脑转移患者的比较疗效。我们使用TriNetX研究网络进行了一项回顾性队列研究，确定了2010年至2024年间诊断为egfr突变型NSCLC和脑转移的成年患者，这些患者接受了奥西替尼。患者被分为在开始使用奥西替尼后6个月内接受RT或SRS的患者（队列1）和单独使用奥西替尼的患者（队列2）。倾向评分匹配（1:1）用于平衡基线特征。主要终点为3年生存率；次要结局包括中枢神经系统并发症、医疗保健利用和二线治疗开始。在743例符合条件的患者中，每个队列匹配217例。队列1的3年生存率显著提高（43% vs 29%; HR 0.67, P = 0.003）。中位生存期分别为25个月和16个月。CNS并发症发生率总体上无显著差异，但排除既往CNS病史的敏感性分析显示，单独使用奥西替尼会增加并发症（HR 2.0, P = .007）。SRS与死亡率降低独立相关（HR 0.49, P = 0.003）。奥西替尼的前期局部治疗可能提高egfr突变NSCLC脑转移患者的生存率，但需要谨慎选择患者。
{"title":"Comparative efficacy of osimertinib with and without radiation therapy in EGFR-mutated nonsmall cell lung cancer with brain metastases","authors":"Rafi Aibani , Jennifer Collins , Amir-Kabirian Borna , Amir Kamran","doi":"10.1016/j.seminoncol.2025.152436","DOIUrl":"10.1016/j.seminoncol.2025.152436","url":null,"abstract":"<div><div>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, <em>P</em> = .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, <em>P</em> = .007). SRS was independently associated with reduced mortality (HR 0.49, <em>P</em> = .003). Upfront local therapy with osimertinib may improve survival in EGFR-mutant NSCLC with brain metastases, though careful patient selection is warranted.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152436"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
口腔癌由于其侵袭性、快速淋巴扩散和有限的治疗选择，仍然是一个主要的临床挑战。尽管诊断和治疗取得了进步，但患者预后仍然很差，迫切需要新的分子靶点。这篇综述系统地研究了钙（Ca 2 +）离子通道，特别是瞬时受体电位（TRP）通道在口腔癌的发生和发展中的关键作用。在Scopus、Embase、Web of Science和谷歌Scholar数据库中进行了截至2025年1月的综合检索。重点关注TRPA1、TRPV1-4、TRPM2、TRPM6和TRPM8通道，强调它们在口腔鳞状细胞癌（OSCC）中的表达失调、功能改变和下游信号传导。越来越多的证据表明，异常的TRP通道活性有助于增强细胞的增殖、迁移、侵袭和存活，从而促进口腔癌的发生。此外，本综述探讨了trp介导的钙信号与PI3K/AKT和MAPK等致癌途径之间的相互作用，阐明了它们对肿瘤行为的共同影响。通过整合分子生物学、药理学和临床研究的见解，这项工作强调了靶向TRP通道作为口腔癌治疗新方法的治疗潜力。未来的研究方向包括描述通道-蛋白质相互作用和开发选择性TRP抑制剂以改善治疗效果。
{"title":"Targeting TRP channels in oral cancer: Mechanistic potential and therapeutic promise","authors":"Kaviyarasi Renu , Vishnu Priya Veeraraghavan , Harishkumar Madhyastha","doi":"10.1016/j.seminoncol.2025.152440","DOIUrl":"10.1016/j.seminoncol.2025.152440","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152440"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-22DOI: 10.1016/j.seminoncol.2025.152427
Abbas Rahdar , Vahideh Mhammadzadeh , Sobia Razzaq , Maryam Shirzad , Sonia Fathi-karkan , Ali Bakhshi , Razieh Behzadmehr , Zelal Kharaba , Luiz Fernando Romanholo Ferreira
Pancreatic disease affects over 10% of the world population, and the most dangerous is pancreatic cancer (PC). The disease is mostly of late age of onset, especially in developed countries, and is associated with poor prognosis due to late presentation. Present screening tests like imaging and biomarkers are insensitive for the high-risk group. Invasive and noninvasive imaging modalities are other diagnostic tests with variable accuracy and accompanying risks. Chemotherapy and surgery are the first lines of treatment, but only 15%–20% of patients are eligible for surgery and the rate of recurrence is very high. Emerging technologies, including physics-informed deep learning (PIDL) and artificial intelligence (AI), are improving early detection techniques by evaluating images and synthesizing data more efficiently. Nanomedicine and AI-driven radiomics are individualizing diagnoses, enhancing drug delivery, and tackling tumor microenvironment issues. Hybrid model methodologies are improving prediction precision in oncology research, while computational drug development and liquid biopsy technologies enable early diagnosis and personalized treatment. The amalgamation of AI, imaging, nanomedicine, and physics-informed models has the potential to transform PC diagnostics, enhancing early detection and patient prognoses.
{"title":"Physics-informed deep learning sharpens nano diagnostics for elusive pancreatic cancer","authors":"Abbas Rahdar , Vahideh Mhammadzadeh , Sobia Razzaq , Maryam Shirzad , Sonia Fathi-karkan , Ali Bakhshi , Razieh Behzadmehr , Zelal Kharaba , Luiz Fernando Romanholo Ferreira","doi":"10.1016/j.seminoncol.2025.152427","DOIUrl":"10.1016/j.seminoncol.2025.152427","url":null,"abstract":"<div><div>Pancreatic disease affects over 10% of the world population, and the most dangerous is pancreatic cancer (PC). The disease is mostly of late age of onset, especially in developed countries, and is associated with poor prognosis due to late presentation. Present screening tests like imaging and biomarkers are insensitive for the high-risk group. Invasive and noninvasive imaging modalities are other diagnostic tests with variable accuracy and accompanying risks. Chemotherapy and surgery are the first lines of treatment, but only 15%–20% of patients are eligible for surgery and the rate of recurrence is very high. Emerging technologies, including physics-informed deep learning (PIDL) and artificial intelligence (AI), are improving early detection techniques by evaluating images and synthesizing data more efficiently. Nanomedicine and AI-driven radiomics are individualizing diagnoses, enhancing drug delivery, and tackling tumor microenvironment issues. Hybrid model methodologies are improving prediction precision in oncology research, while computational drug development and liquid biopsy technologies enable early diagnosis and personalized treatment. The amalgamation of AI, imaging, nanomedicine, and physics-informed models has the potential to transform PC diagnostics, enhancing early detection and patient prognoses.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152427"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-02DOI: 10.1016/j.seminoncol.2025.152454
Amr Ali Mohamed Abdelgawwad El-Sehrawy , Mohammad Y Alshahrani , Muzdalifa Mejbel Fedwi , Subbulakshmi Ganesan , Zahraa Abbas Al-Khafaji , Vimal Arora , Amrita Pal , Priya Priyadarshini Nayak , Sarvar Islomov , Chou-Yi Hsu
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.
{"title":"Immuno-oncology approaches to overcome T cell exhaustion in melanoma","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy , Mohammad Y Alshahrani , Muzdalifa Mejbel Fedwi , Subbulakshmi Ganesan , Zahraa Abbas Al-Khafaji , Vimal Arora , Amrita Pal , Priya Priyadarshini Nayak , Sarvar Islomov , Chou-Yi Hsu","doi":"10.1016/j.seminoncol.2025.152454","DOIUrl":"10.1016/j.seminoncol.2025.152454","url":null,"abstract":"<div><div>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<sup>+</sup>, CD4<sup>+</sup>, and Tregs) in melanoma immunity. CD8<sup>+</sup> 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<sup>+</sup> 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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152454"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-30DOI: 10.1016/j.seminoncol.2025.152434
Ali G. Alkhathami , Abdulrahman T. Ahmed , Ahmed Hussn , S. RenukaJyothi , Rajashree Panigrahi , Hussein Riyadh Abdul Kareem Al-Hetty , Hansi Negi , Pushkar Jassal , Fathi Jihad Hammady , Salah Abdulhadi Salih
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.
{"title":"Nanoparticle-based approaches for doxorubicin delivery in hepatocellular carcinoma: Current strategies and emerging innovations","authors":"Ali G. Alkhathami , Abdulrahman T. Ahmed , Ahmed Hussn , S. RenukaJyothi , Rajashree Panigrahi , Hussein Riyadh Abdul Kareem Al-Hetty , Hansi Negi , Pushkar Jassal , Fathi Jihad Hammady , Salah Abdulhadi Salih","doi":"10.1016/j.seminoncol.2025.152434","DOIUrl":"10.1016/j.seminoncol.2025.152434","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"53 1","pages":"Article 152434"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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