Pub Date : 2025-08-01Epub Date: 2025-06-11DOI: 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
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.
{"title":"Identifying and closing information gaps in head and neck cancer surgery","authors":"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","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}
Pub Date : 2025-08-01Epub Date: 2025-06-11DOI: 10.1016/j.seminoncol.2025.152352
Carla Eksteen , Johann Riedemann , Frederick H. van der Merwe , Matthys H. Botha , Anna-Mart Engelbrecht
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.
{"title":"Advancing personalized medicine in LMICs: Predictive indicators for cervical cancer immunotherapy response","authors":"Carla Eksteen , Johann Riedemann , Frederick H. van der Merwe , Matthys H. Botha , 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}
Pub Date : 2025-08-01Epub Date: 2025-06-18DOI: 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
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.
{"title":"Exosomal circular RNAs as drivers of temozolomide resistance in glioblastoma: Mechanisms and implications","authors":"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","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}
Pub Date : 2025-08-01Epub Date: 2025-06-24DOI: 10.1016/j.seminoncol.2025.152374
Sahil Kumar , Urvashi Gupta , Rajesh Kumar Singh
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.
{"title":"Recent updates on novel heterocyclic scaffolds of anticancer potential as emerging tubulin inhibitors","authors":"Sahil Kumar , Urvashi Gupta , 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}
Pub Date : 2025-08-01Epub Date: 2025-06-25DOI: 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
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.
{"title":"Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment","authors":"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","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}
Pub Date : 2025-08-01Epub Date: 2025-06-20DOI: 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
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.
{"title":"Breast cancer exosomes: Managing macrophage polarization and immune regulation in the tumor microenvironment","authors":"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","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}
Pub Date : 2025-08-01Epub Date: 2025-06-09DOI: 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
Background
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 (A + B) or with Lenvatinib.
Methods
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 (A + B) 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.
Results
919 patients with BCLC-B HCC were analyzed in the study. Lenvatinib was administered to 561 (61%) patients while 358 (39%) received A + B. The median overall survival (mOS) for patients receiving Lenvatinib was 21.3 months compared to 15.8 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B), hazard ratio (HRs) 0.84 P = 0.22. The median time to progression (mTTP) for patients receiving Lenvatinib was 7.3 months compared to 8.7 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B): HR 1.15 P = 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 A + B P < 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 A + B. Favorable prognostic factors for OS in Lenvatinib group were platelets (PLT) >100.000 (HR 0.68 P = 0.02), HCC nonalcoholic steatohepatitis/nonalcoholic fatty liver disease (NASH/NAFLD) related (HR 0.53, P = 0.03). No favorable prognostic factors were found for A + B group. Favorable prognostic factors for TTP in the A + B group were in TACE refractory patients (HR 0.76, P = 0.02), PLT <100.000 (HR 0.62, P = 0.0067), and neutrophil-to-lymphocyte ratio (NLR) < 3 (HR 0.78, P = 0.04).
Conclusion
Although Lenvatinib had a higher response rate, the study showed no statistically significant differences between Lenvatinib and A + B in terms of efficacy, in patients with BCLC-B HCC.
本研究的目的是对巴塞罗那临床肝癌B期（BCLC-B）肝细胞癌（HCC）的大型患者队列进行现实世界的分析，这些患者接受atezolizumab加贝伐单抗（a + B）或Lenvatinib治疗。方法研究人群包括来自东西方人群的不适合局部治疗（LRTs）的巴塞罗那临床肝癌B期（BCLC-B）肝细胞癌患者，他们接受atezolizumab联合贝伐单抗（A + B）或Lenvatinib作为一线治疗。采用单因素和多因素分析评估总生存期（OS）和进展时间（TTP）的预测因素，采用Cox回归模型对预后因素进行单因素和多因素分析。结果本研究共纳入919例BCLC-B型HCC患者。561例（61%）患者服用Lenvatinib， 358例（39%）患者服用A + B。接受Lenvatinib的患者的中位总生存期（mOS）为21.3个月，而一线治疗A + B （Lenvatinib vs A + B）的患者为15.8个月，风险比（hr） 0.84 P = 0.22。接受Lenvatinib的患者的中位进展时间（mTTP）为7.3个月，而一线治疗接受A + B （Lenvatinib vs A + B）的患者为8.7个月：HR 1.15 P = 0.10。多变量分析证实两种治疗在mOS和mTTP方面没有差异。Lenvatinib组患者的客观缓解率（ORR）为47.1%,A + B P <； 0.000001组患者为27.1%。与接受a + B的患者相比，接受Lenvatinib的患者发生手足皮肤反应（HFSR）、高血压、腹泻、疲劳、食欲下降、甲状腺功能减退和其他毒性反应的发生率明显更高。Lenvatinib组OS的有利预后因素为血小板（PLT） > 100,000 (HR 0.68 P = 0.02)，HCC非酒精性脂肪性肝炎/非酒精性脂肪性肝病（NASH/NAFLD）相关（HR 0.53, P = 0.03）。A组 + B组未发现预后有利因素。A + B组TTP的有利预后因素为TACE难治性患者（HR 0.76, P = 0.02），PLT <；10万（HR 0.62, P = 0.0067），中性粒细胞与淋巴细胞比值（NLR） <；3 （hr 0.78, p = 0.04）。结论虽然Lenvatinib的有效率更高，但研究显示Lenvatinib与a + B在BCLC-B HCC患者的疗效方面无统计学差异。
{"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 , 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","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> < 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) >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 <100.000 (HR 0.62, <em>P</em> = 0.0067), and neutrophil-to-lymphocyte ratio (NLR) < 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}
Pub Date : 2025-08-01Epub Date: 2025-06-04DOI: 10.1016/j.seminoncol.2025.152351
Guodong Liang , Yuehan Ma , Ping Deng , Shufeng Li , Chunyan He , Haihang He , Hairui Liu , Yunda Fan , Ze Li
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.
{"title":"Hexokinases in gastrointestinal cancers: From molecular insights to therapeutic opportunities","authors":"Guodong Liang , Yuehan Ma , Ping Deng , Shufeng Li , Chunyan He , Haihang He , Hairui Liu , Yunda Fan , 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}
Pub Date : 2025-06-01Epub Date: 2025-05-24DOI: 10.1016/j.seminoncol.2025.152364
Eyachew Misganew Tegaw , Betelhem Bizuneh Asfaw
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.
{"title":"Explainable machine learning and feature interpretation to predict survival outcomes in the treatment of lung cancer","authors":"Eyachew Misganew Tegaw , 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}
Pub Date : 2025-06-01Epub Date: 2025-05-08DOI: 10.1016/j.seminoncol.2025.152349
Sonia Chadha, Sayali Mukherjee, Somali Sanyal
The complexity and heterogeneity of cancer makes early detection and effective treatment crucial to enhance patient survival and quality of life. The intrinsic creative ability of artificial intelligence (AI) offers improvements in patient screening, diagnosis, and individualized care. Advanced technologies, like computer vision, machine learning, deep learning, and natural language processing, can analyze large datasets and identify patterns that permit early cancer detection, diagnosis, management and incorporation of conclusive treatment plans, ensuring improved quality of life for patients by personalizing care and minimizing unnecessary interventions. Genomics, transcriptomics and proteomics data can be combined with AI algorithms to unveil an extensive overview of cancer biology, assisting in its detailed understanding and will help in identifying new drug targets and developing effective therapies. This can also help to identify personalized molecular signatures which can facilitate tailored interventions addressing the unique aspects of each patient. AI-driven transcriptomics, proteomics, and genomes represents a revolutionary strategy to improve patient outcome by offering precise diagnosis and tailored therapy. The inclusion of AI in oncology may boost efficiency, reduce errors, and save costs, but it cannot take the role of medical professionals. While clinicians and doctors have the final say in all matters, it might serve as their faithful assistant
{"title":"Advancements and implications of artificial intelligence for early detection, diagnosis and tailored treatment of cancer","authors":"Sonia Chadha, Sayali Mukherjee, Somali Sanyal","doi":"10.1016/j.seminoncol.2025.152349","DOIUrl":"10.1016/j.seminoncol.2025.152349","url":null,"abstract":"<div><div>The complexity and heterogeneity of cancer makes early detection and effective treatment crucial to enhance patient survival and quality of life. The intrinsic creative ability of artificial intelligence (AI) offers improvements in patient screening, diagnosis, and individualized care. Advanced technologies, like computer vision, machine learning, deep learning, and natural language processing, can analyze large datasets and identify patterns that permit early cancer detection, diagnosis, management and incorporation of conclusive treatment plans, ensuring improved quality of life for patients by personalizing care and minimizing unnecessary interventions. Genomics, transcriptomics and proteomics data can be combined with AI algorithms to unveil an extensive overview of cancer biology, assisting in its detailed understanding and will help in identifying new drug targets and developing effective therapies. This can also help to identify personalized molecular signatures which can facilitate tailored interventions addressing the unique aspects of each patient. AI-driven transcriptomics, proteomics, and genomes represents a revolutionary strategy to improve patient outcome by offering precise diagnosis and tailored therapy. The inclusion of AI in oncology may boost efficiency, reduce errors, and save costs, but it cannot take the role of medical professionals. While clinicians and doctors have the final say in all matters, it might serve as their faithful assistant</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 3","pages":"Article 152349"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917327","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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