Seminars in oncology最新文献

筛选
英文 中文
Breaking barriers: Deciphering the mechanisms of Olaparib resistance in prostate cancer 突破障碍:解读前列腺癌奥拉帕尼耐药机制
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-26 DOI: 10.1016/j.seminoncol.2025.152375
Amr Ali Mohammed Abdelgawwad Wl-Sehrawy , Mahmood Yaseen Mukhlif , Aysar Ashour Khalaf , Subasini Uthirapathy , Suhas Ballal , Abhayveer Singh , V. Kavitha , Laxmidhar Maharana , Hayder Ridha-Salman , Ahmed Remthan Hussein Al-Altememe
{"title":"Breaking barriers: Deciphering the mechanisms of Olaparib resistance in prostate cancer","authors":"Amr Ali Mohammed Abdelgawwad Wl-Sehrawy ,&nbsp;Mahmood Yaseen Mukhlif ,&nbsp;Aysar Ashour Khalaf ,&nbsp;Subasini Uthirapathy ,&nbsp;Suhas Ballal ,&nbsp;Abhayveer Singh ,&nbsp;V. Kavitha ,&nbsp;Laxmidhar Maharana ,&nbsp;Hayder Ridha-Salman ,&nbsp;Ahmed Remthan Hussein Al-Altememe","doi":"10.1016/j.seminoncol.2025.152375","DOIUrl":"10.1016/j.seminoncol.2025.152375","url":null,"abstract":"<div><div>A poly (ADP-ribose) polymerase (PARP) inhibitor, Olaparib has shown notable clinical effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC) with DNA damage repair gene mutations. Though initial reactions were encouraging, the emergence of resistance poses a major clinical problem that reduces the long-term therapeutic value for patients. This paper thoroughly investigates the molecular processes behind acquired and intrinsic resistance to Olaparib in prostate cancer (PCa). Among the several resistance routes discovered are restoration of homologous recombination (HR) repair capacity via secondary BRCA2 mutations, loss of 53BP1/REV7/Shieldin complex activity, and activation of alternative DNA repair pathways. Recent studies further imply that changes in cell cycle checkpoints and epigenetic changes could help to increase therapy resistance even more. Knowing these several resistance mechanisms helps one to create reasonable combination strategies and biomarker-driven initiatives to defeat Olaparib resistance. Among the new treatment options are combination therapies aimed at compensatory DNA repair mechanisms, cell cycle checkpoint inhibitors, epigenetic modulators, and methods tackling tumor microenvironment elements. Predictive biomarker discovery of resistance will help to guide individual treatment choice and sequential therapy optimization, hence changing clinical results for advanced PCa patients in the precision medicine age.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152375"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480907","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}
引用次数: 0
Identifying and closing information gaps in head and neck cancer surgery 识别和缩小头颈癌手术的信息差距
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1016/j.seminoncol.2025.152362
Sabrina R Comess BA , Justin K Joseph BA , Michelle Yoon BA , Salmaan Sayeed BS , Pranati Borkhetaria BA , Luke Stanisce MD , Margaret Brandwein-Weber MD , Michael Karasick PhD , Mark L Urken MD
{"title":"Identifying and closing information gaps in head and neck cancer surgery","authors":"Sabrina R Comess BA ,&nbsp;Justin K Joseph BA ,&nbsp;Michelle Yoon BA ,&nbsp;Salmaan Sayeed BS ,&nbsp;Pranati Borkhetaria BA ,&nbsp;Luke Stanisce MD ,&nbsp;Margaret Brandwein-Weber MD ,&nbsp;Michael Karasick PhD ,&nbsp;Mark L Urken MD","doi":"10.1016/j.seminoncol.2025.152362","DOIUrl":"10.1016/j.seminoncol.2025.152362","url":null,"abstract":"<div><div>Contemporary cancer management relies on the precise transfer of information regarding disease and treatment details between a range of providers and facilities. The time of surgery is uniquely responsible for many ambiguities in this oncological information flow, as intraoperative communication and documentation are often unregimented and imprecise. Downstream providers such as radiation oncologists, medical oncologists, and radiologists rely on surgical pathology reports for planning postoperative treatment and surveillance. However, traditional pathology reports lack critical details about the actions taken during surgery and do not make the oncologic clearance status explicit. We identified agents of change to improve information transfer and designed an improved surgical workflow and pathology report that make use of a novel pathologic reporting software to address gaps in the oncologic care timeline. Our updated workflow results in a dynamic final pathology report that integrates annotated 3D scans of the surgical specimen and extirpative defect, unequivocal reconciliation of at-risk and supplemental margins, highlighted preoperative radiographs, and brief narrative summaries by the surgeon and pathologist. These tangible changes aim to improve clarity and continuity in oncologic care.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152362"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254034","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}
引用次数: 0
Advancing personalized medicine in LMICs: Predictive indicators for cervical cancer immunotherapy response 在低收入国家推进个体化医疗:宫颈癌免疫治疗反应的预测指标
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1016/j.seminoncol.2025.152352
Carla Eksteen , Johann Riedemann , Frederick H. van der Merwe , Matthys H. Botha , Anna-Mart Engelbrecht
{"title":"Advancing personalized medicine in LMICs: Predictive indicators for cervical cancer immunotherapy response","authors":"Carla Eksteen ,&nbsp;Johann Riedemann ,&nbsp;Frederick H. van der Merwe ,&nbsp;Matthys H. Botha ,&nbsp;Anna-Mart Engelbrecht","doi":"10.1016/j.seminoncol.2025.152352","DOIUrl":"10.1016/j.seminoncol.2025.152352","url":null,"abstract":"<div><div>The World Health Organization reports that cervical cancer ranks as the eighth most common cancer worldwide and is the ninth leading cause of cancer-related deaths. It is also the most prevalent cancer among women in 25 countries, primarily in Sub-Saharan Africa. Consequently, cervical cancer continues to pose a significant global health challenge, particularly due to the limited treatment options available for advanced stages of the disease. Evidently, immunotherapy is a promising strategy, but its efficacy is variable among patients. As such, predictive indicators are essential for identifying patients who are most likely to benefit from immunotherapy and for guiding treatment decisions. This review provides an overview of the current landscape of predictive biomarkers in cervical cancer immunotherapy, including immune checkpoint molecules, tumor mutational burden and immune cell infiltration. We further discuss additional factors such as cytokines, tumor infiltrating lymphocytes and previous exposure to platinum-based chemotherapy. As the field continues to evolve, ongoing research efforts are needed to refine predictive biomarkers and optimize patient selection in LMICs for immunotherapy in cervical cancer.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152352"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254699","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}
引用次数: 0
Exosomal circular RNAs as drivers of temozolomide resistance in glioblastoma: Mechanisms and implications 外泌体环状rna作为胶质母细胞瘤替莫唑胺耐药的驱动因素:机制和意义
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-18 DOI: 10.1016/j.seminoncol.2025.152372
Ehab Yassen Theab , Ali G. Alkhathami , Inas Ridha Ali , Hussein Riyadh Abdul Kareem Al-Hetty , Suhas Ballal , Rishiv Kalia , Sami G. Almalki , Renu Arya , Deepak Nathiya
{"title":"Exosomal circular RNAs as drivers of temozolomide resistance in glioblastoma: Mechanisms and implications","authors":"Ehab Yassen Theab ,&nbsp;Ali G. Alkhathami ,&nbsp;Inas Ridha Ali ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Suhas Ballal ,&nbsp;Rishiv Kalia ,&nbsp;Sami G. Almalki ,&nbsp;Renu Arya ,&nbsp;Deepak Nathiya","doi":"10.1016/j.seminoncol.2025.152372","DOIUrl":"10.1016/j.seminoncol.2025.152372","url":null,"abstract":"<div><div>Glioblastoma (GBM) continues to be 1 of the most malignant tumors with limited success in therapy, primarily owing to the emergence of resistance towards temozolomide TMZ. Resistance to TMZ is a multifactorial phenomenon in GBM, depending on the interactions between genetic, epigenetic, and microenvironmental factors. Noncoding RNAs, most significantly circRNAs, have recently been highlighted as playing important roles in the pathogenesis of GBM and drug resistance against TMZ. These stable, circular RNA molecules can act as microRNA sponges or encode functional peptides; hence, they modulate functions relating to different aspects of tumor development. Furthermore, circRNAs can be carried within exosomes, promoting intercellular communication and propagation of drug resistance. Exosomes serve as sophisticated delivery vehicles that harbor varying bioactive molecules like proteins, lipids, mRNAs, miRNAs, lncRNAs, and many others, including circular RNAs. This review elucidates the specific functions held by exosomal circRNAs, such as circASAP1 and circ-HIPK3, in the modulation of TMZ resistance through different molecular pathways. It also reflects the biomarker potential of exosomal circRNAs as diagnostics and prognostics, allowing their dynamic application in liquid biopsies to monitor the progression of GBM over time. This review tries to develop an understanding of the complex nature of mechanisms conferring resistance to TMZ, with a particular focus on new insights regarding the potential roles of exosomal circular RNAs.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152372"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313673","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}
引用次数: 0
Recent updates on novel heterocyclic scaffolds of anticancer potential as emerging tubulin inhibitors 新型杂环支架作为新兴微管蛋白抑制剂抗癌潜力的最新进展
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-24 DOI: 10.1016/j.seminoncol.2025.152374
Sahil Kumar , Urvashi Gupta , Rajesh Kumar Singh
{"title":"Recent updates on novel heterocyclic scaffolds of anticancer potential as emerging tubulin inhibitors","authors":"Sahil Kumar ,&nbsp;Urvashi Gupta ,&nbsp;Rajesh Kumar Singh","doi":"10.1016/j.seminoncol.2025.152374","DOIUrl":"10.1016/j.seminoncol.2025.152374","url":null,"abstract":"<div><div>Cancer remains a leading cause of mortality worldwide, accounting for approximately one in six deaths. Among the most prevalent cancer types are prostate, lung, colon, and rectal cancers. Despite significant investments in research, the therapeutic success of modern cancer treatments remains limited compared to other life-threatening diseases. In the pursuit of novel anticancer strategies, microtubules—dynamic cytoskeletal structures essential for cellular processes such as mitosis, intracellular transport, and signaling—have emerged as attractive drug targets. This review provides a comprehensive overview of recent advancements in the design and synthesis of novel heterocyclic scaffolds as tubulin inhibitors, emphasizing their potential as anticancer agents. Heterocyclic compounds exhibit unique therapeutic properties that disrupt microtubule dynamics, inducing cell cycle arrest and apoptosis in rapidly proliferating cancer cells. The article systematically classifies and critically evaluates diverse heterocyclic scaffolds, including both natural products and synthetic derivatives, with a focus on their interactions with the microtubule cytoskeleton at a molecular level. By consolidating current insights into these emerging scaffolds, this review serves as a valuable resource for the development of next-generation anticancer therapeutics targeting tubulin.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152374"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472025","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}
引用次数: 0
Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment 我们到了吗?肠道菌群对癌症的诊断、预后和治疗
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-25 DOI: 10.1016/j.seminoncol.2025.152376
Carlos Ordóñez , Sara Zurita , Giuliana Ramírez , Fernanda Cordeiro , Katherine Garcia-Matamoros , Fuad Huaman-Garaicoa , Andrea Orellana-Manzano , Lorena Sandoya-Onofre , Juan Pogo , Diana Carvajal-Aldaz
{"title":"Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment","authors":"Carlos Ordóñez ,&nbsp;Sara Zurita ,&nbsp;Giuliana Ramírez ,&nbsp;Fernanda Cordeiro ,&nbsp;Katherine Garcia-Matamoros ,&nbsp;Fuad Huaman-Garaicoa ,&nbsp;Andrea Orellana-Manzano ,&nbsp;Lorena Sandoya-Onofre ,&nbsp;Juan Pogo ,&nbsp;Diana Carvajal-Aldaz","doi":"10.1016/j.seminoncol.2025.152376","DOIUrl":"10.1016/j.seminoncol.2025.152376","url":null,"abstract":"<div><div>Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognosis, and treatment outcomes. This review analyzes observational and interventional studies conducted with human subjects over the past 5 years, highlighting significant advancements in gut microbiota research for cancer management. Observational studies consistently demonstrated differences in gut microbial composition between cancer patients and healthy controls. Moreover, microbial diversity, particularly at the species and strain level, correlated significantly with clinical outcomes. Interventional studies showed the potential of probiotics and fecal microbiota transplantation (FMT) as adjuncts in cancer therapy by restoring microbial diversity, reducing inflammation, and alleviating chemotherapy-induced complications. Collectively, these findings suggest the gut microbiota’s potential as a tool for cancer care. Future research should focus on standardizing taxonomic-level analyses, optimizing probiotic formulations, and validating FMT/AFMT clinical protocols to fully harness the gut microbiota’s diagnostic and therapeutic capabilities in oncology.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152376"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472024","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}
引用次数: 0
Breast cancer exosomes: Managing macrophage polarization and immune regulation in the tumor microenvironment 乳腺癌外泌体:在肿瘤微环境中管理巨噬细胞极化和免疫调节
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-20 DOI: 10.1016/j.seminoncol.2025.152365
Suleiman Ibrahim Mohammad , Ehab Yassen Theab , Asokan Vasudevan , Ashok Kumar Bishoyi , Suhas Ballal , Hussein Riyadh Abdul Kareem Al-Hetty , Aman Shankhyan , Anupria A , Rajashree Panigrahi , Hatif Abdulrazaq Yasin
{"title":"Breast cancer exosomes: Managing macrophage polarization and immune regulation in the tumor microenvironment","authors":"Suleiman Ibrahim Mohammad ,&nbsp;Ehab Yassen Theab ,&nbsp;Asokan Vasudevan ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;Suhas Ballal ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Aman Shankhyan ,&nbsp;Anupria A ,&nbsp;Rajashree Panigrahi ,&nbsp;Hatif Abdulrazaq Yasin","doi":"10.1016/j.seminoncol.2025.152365","DOIUrl":"10.1016/j.seminoncol.2025.152365","url":null,"abstract":"<div><div>Exosomes are sub-150 nm extracellular vesicles mediating intercellular messaging in breast cancer's complex tumor microenvironment (TME). Produced by both tumor cells and their stroma components, these vesicles excrete various biomolecules, such as microRNAs (miRNAs), proteins, lipids, and even DNA fragments, enabling a functional exchange of information among cells. In breast cancer, different studies indicate a significant role of exosome-mediated signaling in modulating the phenotype of tumor-associated macrophages (TAMs), mainly polarizing them toward an M2-like phenotype, further supporting the potentiality for tumor-promoting functions. This review will detail the diverse roles of breast cancer-derived exosomes and macrophage polarization and elaborate on their recognized pathways by which these vesicles casually alter the macrophage phenotype. In our discussion, we take a broad detour to deeply examine the unique molecular accessories delivered by breast cancer exosomes. In particular, we discuss the miRNAs suppressed by M1-associated gene expression and those endowing M2-related pathways with abilities, and we cover the proteins that activate pathways like the STAT3 and NF-κB pathways in macrophages. This review will also address the relevance of mechanistic issues to clinical manifestation in exosome-mediated macrophage polarization in breast cancer. Finally, targeting exosome-mediated macrophage polarization as a promising strategy to enhance antitumor immunity in conjunction with improving breast cancer outcomes is deliberated.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152365"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322977","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}
引用次数: 0
Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population Atezolizumab联合贝伐单抗与Lenvatinib治疗巴塞罗那临床肝癌B期(BCLC-B)肝细胞癌(HCC)患者:现实世界人群
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1016/j.seminoncol.2025.152348
Francesco Vitiello , Toshifumi Tada , Goki Suda , Shigeo Shimose , Masatoshi Kudo , Jaekyung Cheon , Fabian Finkelmeier , Ho Yeong Lim , José Presa , Gianluca Masi , Changhoon Yoo , Sara Lonardi , Francesco Tovoli , Takashi Kumada , Mario Scartozzi , Emiliano Tamburini , Francesco Giuseppe Foschi , Mara Persano , Federico Rossari , Silvia Foti , Margherita Rimini
{"title":"Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population","authors":"Francesco Vitiello ,&nbsp;Toshifumi Tada ,&nbsp;Goki Suda ,&nbsp;Shigeo Shimose ,&nbsp;Masatoshi Kudo ,&nbsp;Jaekyung Cheon ,&nbsp;Fabian Finkelmeier ,&nbsp;Ho Yeong Lim ,&nbsp;José Presa ,&nbsp;Gianluca Masi ,&nbsp;Changhoon Yoo ,&nbsp;Sara Lonardi ,&nbsp;Francesco Tovoli ,&nbsp;Takashi Kumada ,&nbsp;Mario Scartozzi ,&nbsp;Emiliano Tamburini ,&nbsp;Francesco Giuseppe Foschi ,&nbsp;Mara Persano ,&nbsp;Federico Rossari ,&nbsp;Silvia Foti ,&nbsp;Margherita Rimini","doi":"10.1016/j.seminoncol.2025.152348","DOIUrl":"10.1016/j.seminoncol.2025.152348","url":null,"abstract":"<div><h3>Background</h3><div>The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (<em>A</em> + <em>B</em>) or with Lenvatinib.</div></div><div><h3>Methods</h3><div>The study population included patients affected with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma not suitable for locoregional therapies (LRTs) from eastern and western populations, who received atezolizumab plus bevacizumab (<em>A</em> + <em>B</em>) or Lenvatinib as first-line treatment. Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and time to progression (TTP) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model.</div></div><div><h3>Results</h3><div>919 patients with BCLC-B HCC were analyzed in the study. Lenvatinib was administered to 561 (61%) patients while 358 (39%) received <em>A</em> + <em>B</em>. The median overall survival (mOS) for patients receiving Lenvatinib was 21.3 months compared to 15.8 months for patients receiving <em>A</em> + <em>B</em> as first-line treatment (Lenvatinib <em>v A</em> + <em>B</em>), hazard ratio (HRs) 0.84 <em>P</em> = 0.22. The median time to progression (mTTP) for patients receiving Lenvatinib was 7.3 months compared to 8.7 months for patients receiving <em>A</em> + <em>B</em> as first-line treatment (Lenvatinib <em>v A</em> + <em>B</em>): HR 1.15 <em>P</em> = 0.10. Multivariate analysis confirmed no different in terms of mOS and mTTP between the two treatments. Objective response rate (ORR) was 47.1% for patients receiving Lenvatinib and 27.1% for patients receiving <em>A</em> + <em>B P</em> &lt; 0.000001. Patients receiving Lenvatinib experienced a significantly higher incidence of hand-foot skin reaction (HFSR), hypertension, diarrhea, fatigue, decrease appetite, hypothyroidism, and other toxicity compared to patients receiving <em>A</em> + <em>B</em>. Favorable prognostic factors for OS in Lenvatinib group were platelets (PLT) &gt;100.000 (HR 0.68 <em>P</em> = 0.02), HCC nonalcoholic steatohepatitis/nonalcoholic fatty liver disease (NASH/NAFLD) related (HR 0.53, <em>P</em> = 0.03). No favorable prognostic factors were found for <em>A</em> + <em>B</em> group. Favorable prognostic factors for TTP in the <em>A</em> + <em>B</em> group were in TACE refractory patients (HR 0.76, <em>P</em> = 0.02), PLT &lt;100.000 (HR 0.62, <em>P</em> = 0.0067), and neutrophil-to-lymphocyte ratio (NLR) &lt; 3 (HR 0.78, <em>P</em> = 0.04).</div></div><div><h3>Conclusion</h3><div>Although Lenvatinib had a higher response rate, the study showed no statistically significant differences between Lenvatinib and <em>A</em> + <em>B</em> in terms of efficacy, in patients with BCLC-B HCC.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152348"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240330","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}
引用次数: 0
Hexokinases in gastrointestinal cancers: From molecular insights to therapeutic opportunities 己糖激酶在胃肠道癌症中的作用:从分子观察到治疗机会
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1016/j.seminoncol.2025.152351
Guodong Liang , Yuehan Ma , Ping Deng , Shufeng Li , Chunyan He , Haihang He , Hairui Liu , Yunda Fan , Ze Li
{"title":"Hexokinases in gastrointestinal cancers: From molecular insights to therapeutic opportunities","authors":"Guodong Liang ,&nbsp;Yuehan Ma ,&nbsp;Ping Deng ,&nbsp;Shufeng Li ,&nbsp;Chunyan He ,&nbsp;Haihang He ,&nbsp;Hairui Liu ,&nbsp;Yunda Fan ,&nbsp;Ze Li","doi":"10.1016/j.seminoncol.2025.152351","DOIUrl":"10.1016/j.seminoncol.2025.152351","url":null,"abstract":"<div><div>Hexokinases (HKs) catalyze the first step in glycolysis by transferring a phosphate group to glucose to produce glucose-6-phosphate (G6P); dysregulation of HKs is a feature that leads to altered metabolism within gastrointestinal (GI) cancers—namely, gastric, colorectal, esophageal, and pancreatic cancer. Of note, HKs have been found to exert non-canonical roles beyond metabolism, particularly in regulating cell death pathways such as autophagy and apoptosis in these cancers. In this sense, HK2 promotes hepatocellular carcinoma (HCC) from apoptosis inhibition through the suppression of mitochondrial permeability transition pore formation by interaction with voltage-dependent anion channel (VDAC). Moreover, HK2 expression in HCC tumors decreases immune responsiveness and sensitivity to natural killer (NK) cytotoxicity, thus favoring immune escape. HK2 and co-expressed genes participate in esophageal cancer (ESCA) microenvironment immune response, especially in B cells, CD4 T cells, and macrophages. Most importantly, 3-BP, an HK-2 inhibitor, induces endoplasmic reticulum (ER) stress and disruption of the ER function by the accumulation of free radicals or reactive oxygen species (ROS) and the protein misfolding, thereby causing apoptosis in human HCC. Of note, it has been found that interaction of HK domain containing protein-1 (HKDC1) with ACTA2 (actin alpha 2) is required for the association of signal transducer and activator of transcription 1 (STAT1) with interferon-gamma receptor (IFNG-R) on the plasma membrane, STAT1-phosphorylation, and thus programmed cell death ligand 1 (PD-L1) expression upon stimulation with IFNγ in HCC. This review summarizes the mechanistic involvement of HKs in glycolytic reprogramming, apoptotic resistance, autophagy, immune evasion, metastasis, and drug resistance in GI cancers and the potential of HKs as diagnostic and therapeutic targets.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 4","pages":"Article 152351"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212884","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}
引用次数: 0
Explainable machine learning and feature interpretation to predict survival outcomes in the treatment of lung cancer 可解释的机器学习和特征解释预测肺癌治疗的生存结果
IF 3 3区 医学
Seminars in oncology Pub Date : 2025-06-01 Epub Date: 2025-05-24 DOI: 10.1016/j.seminoncol.2025.152364
Eyachew Misganew Tegaw , Betelhem Bizuneh Asfaw
{"title":"Explainable machine learning and feature interpretation to predict survival outcomes in the treatment of lung cancer","authors":"Eyachew Misganew Tegaw ,&nbsp;Betelhem Bizuneh Asfaw","doi":"10.1016/j.seminoncol.2025.152364","DOIUrl":"10.1016/j.seminoncol.2025.152364","url":null,"abstract":"<div><div>The treatment outcomes of lung cancer are highly variable, and machine learning (ML) models provide valuable insights into how clinical and biochemical factors influence survival across different treatments. This study will investigate the survival of patients after four major treatments for lung cancer by interpreting the impact of biomarkers on survival using SHapley Additive exPlanations (SHAP). We analyzed 23,658 lung cancer patient records derived from a Kaggle dataset. Using the most relevant clinical and biochemical variables, ML models were employed to study survival outcomes for different treatments. SHAP analysis revealed major survival predictors in each treatment. Survival outcomes are visualized as f(x) (predicted survival) and E[f(x)] (baseline expectation) in SHAP waterfall plots. The most performed model is Gradient Boosting with an accuracy of 88.99%, precision of 89.06%, recall of 88.99%, F1-score of 88.91%, and Receiver Operating Characteristic Curve (AUC-ROC) score of 0.9332. Chemotherapy treatment was positive for survival, the key for survival was phosphorus levels (+0.05), low Alanine Aminotransferase levels (+0.04) and low glucose levels (+0.04). Targeted therapy and radiation had worse survival, while surgery was favorable, especially in cases with high white blood cell and Lactate Dehydrogenase (LDH) levels. SHAP-based ML analysis aptly underlines how clinical and biochemical factors influence the survival rate. It indicates that ML-driven interpretability might drive personalized treatment approaches in lung cancer.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 3","pages":"Article 152364"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125323","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书