Mahir Azmal, Md. Munna Miah, Fatema Sultana Prima, Jibon Kumar Paul, ANM Shah Newaz Been Haque, Ajit Ghosh
{"title":"Advances and challenges in cancer immunotherapy: Strategies for personalized treatment","authors":"Mahir Azmal, Md. Munna Miah, Fatema Sultana Prima, Jibon Kumar Paul, ANM Shah Newaz Been Haque, Ajit Ghosh","doi":"10.1016/j.seminoncol.2025.152345","DOIUrl":"10.1016/j.seminoncol.2025.152345","url":null,"abstract":"<div><div>Cancer immunotherapy has transformed oncology by harnessing the immune system to specifically target cancer cells, offering reduced systemic toxicity compared to traditional therapies. This review highlights key strategies, including adoptive cell transfer (ACT), immune checkpoint inhibitors, oncolytic viral (OV) therapy, monoclonal antibodies (mAbs), and mRNA-based vaccines. ACT reinfuses enhanced immune cells like tumor-infiltrating lymphocytes (TILs) to combat refractory cancers, while checkpoint inhibitors (eg, PD-1 and CTLA-4 blockers) restore T-cell activity. OV therapy uses engineered viruses (eg, T-VEC) to selectively lyse cancer cells, and advanced mAbs improve targeting precision. mRNA vaccines introduce tumor-specific antigens to trigger robust immune responses. Despite significant progress, challenges like immune-related side effects, high costs, and immunosuppressive tumor microenvironments persist. This review underscores the need for combination strategies and precision medicine to overcome these barriers and maximize the potential of immunotherapy in personalized cancer treatment.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 3","pages":"Article 152345"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881725","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}
{"title":"Epidemiology and prevention of gastric cancer: A comprehensive review","authors":"Smruti Priyambada Pradhan , Ayushman Gadnayak , Sukanta Kumar Pradhan , Venkatarao Epari","doi":"10.1016/j.seminoncol.2025.152341","DOIUrl":"10.1016/j.seminoncol.2025.152341","url":null,"abstract":"<div><div>Gastric cancer is the third most deadly cancer worldwide. <em>Helicobacter pylori</em> (<em>H. pylori</em>) infection and specific diets are key risk factors for this illness, which is more frequent in various nations. Nearly half of the world's population, 4.4 billion, had <em>H. pylori</em> in 2015. East has a higher incidence rate than West. GC may spread to the liver, lungs, and bones. The majority of cases are adenocarcinomas (90%). In 2022, stomach cancer caused 968,784 new cases and 660,175 deaths worldwide. GC accounts for 7% of cancer diagnoses and 9% of deaths. The high death rate of gastric cancer highlights the need for preventative methods to improve prognosis. Early identification via biomarker screening, especially in high-risk groups, may improve outcomes and treatments.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 3","pages":"Article 152341"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881798","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}
Yang Wu , Chun Zhang , Jiacheng Huang , Qun Chen , Yufeng Zhang , Fengyuan Liu , Dong Xu , Kuirong Jiang , Run Shi , Mengxing Chen , Hao Yuan
{"title":"Integrated analysis of scRNA-seq and bulk RNA-seq data identifies BHLHE40 as a key gene in pancreatic cancer progression and gemcitabine resistance","authors":"Yang Wu , Chun Zhang , Jiacheng Huang , Qun Chen , Yufeng Zhang , Fengyuan Liu , Dong Xu , Kuirong Jiang , Run Shi , Mengxing Chen , Hao Yuan","doi":"10.1016/j.seminoncol.2025.152338","DOIUrl":"10.1016/j.seminoncol.2025.152338","url":null,"abstract":"<div><h3>Objective</h3><div>Pancreatic cancer is characterized by its high mortality rate and short survival periods, and novel therapeutic targets and tailor personalized strategies are urgently needed. In this study, we aim to investigate the molecular mechanisms underlying pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance, with a focus on identifying novel therapeutic targets.</div></div><div><h3>Methods</h3><div>Multiomics approaches were integrated to identify novel actionable targets for PDAC. Public datasets such as TCGA and GEO were utilized to investigate the relationship between gene expression and clinical outcomes. Functional enrichment, cell-cell communication, and metabolic pathway analyses were performed to reveal PDAC heterogeneity and therapeutic resistance mechanisms.</div></div><div><h3>Results</h3><div>BHLHE40 was identified as a hub gene linked to high-CNV PDAC cells, Gemcitabine resistance, and poor prognosis in PDAC. High BHLHE40 expression is significantly correlated with immunosuppressive tumor microenvironment (TME) features such as reduced CD8+ <em>T</em> infiltration, TCR richness, and lower tumor mutational burden (TMB). ChIP-seq data analysis confirmed BHLHE40 could directly bind to the SAT1 promoter, establishing a transcriptional axis promoting chemoresistance. Single-cell RNA-seq analysis further revealed that the BHLHE40+/SAT1+ subpopulation cells are resistant to Gemcitabine in PDAC.</div></div><div><h3>Conclusions</h3><div>BHLHE40 is significantly correlated with PDAC malignancy and chemoresistance via SAT1 regulation and immune evasion. Targeting BHLHE40 may sensitize PDACs to Gemcitabine and facilitate personalized treatment for BHLHE40+ PDAC patients.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152338"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839185","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}
{"title":"The interest of therapeutic and pharmacological drug monitoring of methotrexate: A systematic review","authors":"Wissal Chellal , Youssra Metarfi , Zineb Ben khadda , Hasnae Hoummani , Rhizlane Berrady , Sanae Achour","doi":"10.1016/j.seminoncol.2025.152342","DOIUrl":"10.1016/j.seminoncol.2025.152342","url":null,"abstract":"<div><div>Methotrexate (MTX) is largely prescribed for cancers, particularly hematological malignancies. To reduce its toxicity, therapeutic drug monitoring (TDM) is highly recommended. This review aimed to assess knowledge on methotrexate monitoring and compare strategies for managing its toxicities. We searched several databases for articles that met the selection criteria. All articles were screened and data on analytical methods, results, and toxicities were extracted. Thirty articles were included in this review, consisting mainly of single-center studies. MTX monitoring studies have been conducted in various countries. Patient demographics covered children and adults, with one study focusing on elderly patients. MTX doses varied primarily between high-dose regimens. Sample collection times were varied. Various techniques were used to quantify MTX levels. This review highlights the diversity of study designs, patient populations, dosing regimens, and analytical techniques, emphasizing the need for standardized protocols and further research to optimize MTX treatment, ensuring both efficacy and safety.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152342"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833360","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}
{"title":"Liquid biopsy: An innovative tool in oncology. Where do we stand?","authors":"Serafina Martella , Demi Wekking , Eleonora Lai , Matteo Lambertini , Angela Pettinato , Alissa Parrino , Francesca Semonella , Giorgia Sanna , Antonio Maccioni , Mario Scartozzi , Alfredo Addeo , Cinzia Solinas","doi":"10.1016/j.seminoncol.2025.152343","DOIUrl":"10.1016/j.seminoncol.2025.152343","url":null,"abstract":"<div><div>The Liquid Biopsy (LB) represents an ideal surrogate of tumor Tissue Biopsy (TB) when the aim is to obtain useful information on patient prognosis and personalized therapy. This technique renders it possible to isolate circulating tumor cells, circulating tumor DNA and other molecules from biological fluids. The most commonly used fluid for liquid biopsy is blood, but depending on the case it could be necessary to isolate the tumor components from other biological fluids such as urine, pleural effusion, cerebrospinal fluid, and others. The main advantages of liquid biopsy are the minimally invasive nature of the procedure and the possibility of analyzing all tumor clones. Limitations include difficulties in the isolation of tumor components and the requirement for highly sensitive analysis methods to avoid the risk of technical artifacts. In our review we will focus on describing circulating tumor biomarkers to illustrate the variety of information that can be obtained from biological fluids, particularly blood. We will then discuss the advanced biotechnological techniques suitable for the identification and analysis of Circulating Tumor DNA (ctDNA), examining both the potential and limitations of analytical methods and the clinical applicability of liquid biopsy for cancer diagnosis, monitoring, and therapeutic prediction. Additionally, we will explore strategies to enhance this valuable alternative to the more invasive tissue biopsy, with a dedicated focus on ongoing clinical studies, currently approved tests, and guideline recommendations.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152343"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825489","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}
{"title":"Circular RNAs: Emerging regulators of signaling pathways in epithelial-mesenchymal transition and angiogenesis during breast cancer progression","authors":"Nivruthi Sasi, Dilipkumar Preetha, Saranya Iyyappan, Nagarajan Selvamurugan","doi":"10.1016/j.seminoncol.2025.152340","DOIUrl":"10.1016/j.seminoncol.2025.152340","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) have emerged as important regulators of gene expression and cellular activities, and abnormalities in circRNAs in breast cancer have been linked to important biological processes like epithelial-mesenchymal transition (EMT) and angiogenesis, both essential for tumor metastasis. EMT facilitates the transition of epithelial cancer cells into a mesenchymal phenotype, enhancing their invasive and migratory capabilities, while angiogenesis promotes tumor progression by forming new blood vessels. CircRNAs also interact with microRNAs to regulate signaling pathways such as TGF-β, Wnt/-catenin, and VEGF. Besides EMT and angiogenesis, studies have identified that circRNAs affect metabolic reprogramming, chemoresistance, tumor microenvironment remodeling, and immunological evasion. Thus, circRNAs play a multifaceted role in the development of breast cancer. They hold potential as non-invasive biomarkers and therapeutic targets due to their high stability, resistance to exonuclease degradation, abundance in body fluids, and diverse expression patterns across different tissues. This review summarizes and critically assesses existing understanding of the functional roles and molecular processes of circRNAs in controlling EMT and angiogenesis during breast cancer progression.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152340"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821058","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}
{"title":"Exploring the clinical trials, regulatory insights, and challenges of PROTACs in oncology","authors":"Sowndharya M , Ramesh Joga , Kajal Gandhi , Sravani Yerram , Rajeev Singh Raghuvanshi , Saurabh Srivastava","doi":"10.1016/j.seminoncol.2025.152339","DOIUrl":"10.1016/j.seminoncol.2025.152339","url":null,"abstract":"<div><div>While various targeted therapies exist for cancer, resistance mechanisms remain a significant challenge. Recent advancements in cancer treatment have led to the emergence of proteolysis-targeting chimeras (PROTACs), a promising technology utilizing hetero-bifunctional molecules to target and degrade proteins implicated in cancer progression through the ubiquitin-proteasome system (UPS). PROTACs offer a novel approach, with recent studies and clinical trials demonstrating promising outcomes in degrading endogenous proteins linked to cancer. This work explores classification, regulatory approvals, and ongoing clinical trials of PROTAC technology in cancer management. It emphasizes the importance of regulatory compliance to expedite approvals from relevant authorities. It also highlights challenges and opportunities associated with their implementation. Despite these preliminary efforts, PROTACs show immense potential in effectively addressing cancer. Their ability to target specific proteins for degradation represents a significant advancement in cancer therapeutics, offering new hope for improved outcomes in patient care.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152339"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847505","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}
{"title":"High tumor mutation burden mitigates the negative impact of chemotherapy history on immune checkpoint blockade therapy","authors":"Ming Zheng MD, PhD","doi":"10.1053/j.seminoncol.2025.01.003","DOIUrl":"10.1053/j.seminoncol.2025.01.003","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC. ICI therapy has revolutionized treatment, but prior chemotherapy may diminish ICI treatment efficacy. Tumor mutation burden (TMB) has emerged as a crucial predictor of ICI response, yet its interaction with chemotherapy history in ICI therapy is not fully understood. In this study, I investigate the impact of chemotherapy history on ICI treatment outcomes, focusing on TMB as a potential mitigating factor. Analyzing data from 512 patients with advanced NSCLC treated with PD-1/PD-L1 or CTLA-4 inhibitors, this sudy found that prior chemotherapy significantly reduced objective response rates (ORR) to ICI therapy, particularly in patients with low TMB (<15 mut/Mb). However, in patients with high TMB (≥15 mut/Mb), the negative impact of chemotherapy history on ICI treatment efficacy is minimal, suggesting that high TMB mitigates chemotherapy-induced resistance to ICI therapy. Furthermore, while chemotherapy history is associated with worse overall survival (OS) and progression-free survival (PFS) following ICI therapy in low-TMB patients, no such association is observed in high-TMB patients. These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152334"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601473","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}
Chengu Niu , Jing Zhang , Patrick I. Okolo III , Ebubekir Daglilar
{"title":"Plant polyphenols in gastric cancer: Nature's healing touch","authors":"Chengu Niu , Jing Zhang , Patrick I. Okolo III , Ebubekir Daglilar","doi":"10.1053/j.seminoncol.2025.01.002","DOIUrl":"10.1053/j.seminoncol.2025.01.002","url":null,"abstract":"<div><div>Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152333"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592491","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}
{"title":"Fingerprint change as a consequence of anticancer treatments: A systematic integrative review","authors":"Silvia Belloni , Arianna Magon , Rita de Sanctis , Paola Tiberio , Gianluca Conte , Cristina Arrigoni , Rosario Caruso","doi":"10.1016/j.seminoncol.2025.152335","DOIUrl":"10.1016/j.seminoncol.2025.152335","url":null,"abstract":"<div><h3>Objective</h3><div>While it is widely acknowledged that fingerprint recognition has played an essential part in policing and forensic science, little is known about fingerprint alterations in medical science, specifically as a consequence of anticancer treatments. Thus, we aimed to analyze the extent of evidence between cancer treatments and fingerprint alterations in adults with cancer.</div></div><div><h3>Methods</h3><div>A systematic integrative review was conducted according to the PRISMA statement and the Cochrane guidelines for conducting a systematic review. PubMed, CINAHL, Web of Science, and Scopus were searched from the inception between August and November 2024. The quality appraisal was conducted to evaluate the methodological quality of the included articles, selecting the most appropriate tool based on the publication type and study design.</div></div><div><h3>Results</h3><div>Of 176 records, we selected five experimental studies articles and nine case reports publications. A correlation between specific anticancer treatments (capecitabine, taxanes, and tyrosine kinase inhibitors) and fingerprint alterations has been documented in individuals with various cancer diagnoses (mainly advanced breast and colorectal cancers). The majority of articles were of moderate to low quality.</div></div><div><h3>Conclusions</h3><div>Although fingerprint alteration as a consequence of specific anticancer treatments has been documented, further large and well-designed experimental studies are necessary to quantify the phenomenon burden in relation to specific anticancer regimens and populations.</div></div><div><h3>Prospero registration n</h3><div>(CRD42024581192).</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 41-54"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}