Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104589
QingQing Luo , LiLi Zhou , DaYa Luo , Li Yu
Clonal hematopoiesis (CH) typically refers to the clonal expansion of hematopoietic stem cells (HSCs) due to genetic mutations, serving as the pathogenic basis for various diseases. Clonal hematopoiesis of indeterminate potential (CHIP) is a subtype of CH, emerging as a significant risk factor for myeloid malignancies and cardiovascular diseases, which has attracted increasing attention. However, recent research has unveiled previously overlooked links between CHIP and lymphoma. This paper reviews the relationship between CHIP and lymphoma, focusing on the role and mechanism of TET2 and DNMT3A-mediated CHIP in lymphoma from the perspective of laboratory research and clinical observation. Additionally, we explore the therapeutic implications of targeting CHIP genes and inflammatory pathways in lymphoma. Our findings underscore the multifaceted influence of CHIP on lymphoma development and provide a promising avenue for therapeutic interventions in CHIP mediated lymphoma.
{"title":"Clonal hematopoiesis of indeterminate potential (CHIP): A potential contributor to lymphoma","authors":"QingQing Luo , LiLi Zhou , DaYa Luo , Li Yu","doi":"10.1016/j.critrevonc.2024.104589","DOIUrl":"10.1016/j.critrevonc.2024.104589","url":null,"abstract":"<div><div>Clonal hematopoiesis (CH) typically refers to the clonal expansion of hematopoietic stem cells (HSCs) due to genetic mutations, serving as the pathogenic basis for various diseases. Clonal hematopoiesis of indeterminate potential (CHIP) is a subtype of CH, emerging as a significant risk factor for myeloid malignancies and cardiovascular diseases, which has attracted increasing attention. However, recent research has unveiled previously overlooked links between CHIP and lymphoma. This paper reviews the relationship between CHIP and lymphoma, focusing on the role and mechanism of TET2 and DNMT3A-mediated CHIP in lymphoma from the perspective of laboratory research and clinical observation. Additionally, we explore the therapeutic implications of targeting CHIP genes and inflammatory pathways in lymphoma. Our findings underscore the multifaceted influence of CHIP on lymphoma development and provide a promising avenue for therapeutic interventions in CHIP mediated lymphoma.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104589"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104597
Jaber H. Jaradat , Ibraheem M. Alkhawaldeh , Yousef Al-Bojoq , Monther N. Ramadan , Mohammad T. Abuawwad , Yasmeen Jamal Alabdallat , Abdulqadir J. Nashwan
Background
Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.
Objectives
This systematic review and meta-analysis aimed to evaluate the safety and efficacy of ibrutinib in the treatment of CNSL, focusing on overall response (OR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events.
Methods
A comprehensive search of the PubMed, Google Scholar, and Scopus databases was conducted. The included studies were prospective and retrospective studies focusing on ibrutinib as monotherapy or in combination with CNSL. Data extraction and quality assessment were independently performed by two reviewers, and statistical analyses were conducted using R version 4.4.0.
Results
Fourteen studies (eight cohort studies and six clinical trials) involving 784 patients were included. The median age was 61 years, with nearly equal sex distribution. The meta-analysis for CNSL, the partial response rate was 29.52 %, complete response rate was 49.19 %, and overall response rate was 72.11 %. For PCNSL, the partial response rate was 20.85 %, complete response rate was 48.13 %, and overall response rate was 66.92 %. For SCNSL, the partial response rate was 29.42 %, complete response rate was 44.64 %, and overall response rate was 66.82 %. Significant heterogeneity was observed in some comparisons. There were no significant differences in the efficacy of ibrutinib between CNSL subtypes.
Conclusions
Ibrutinib shows promising efficacy in improving partial and complete response rates in CNSL. The substantial heterogeneity observed underscores the need for further well-designed studies to confirm these findings and explore the optimal use of ibrutinib in CNSL treatment protocols. Future trials should consider comparing ibrutinib to standard therapies and investigate its long-term efficacy and safety profile.
{"title":"Efficacy and safety of ibrutinib in central nervous system lymphoma: A systematic review and meta-analysis","authors":"Jaber H. Jaradat , Ibraheem M. Alkhawaldeh , Yousef Al-Bojoq , Monther N. Ramadan , Mohammad T. Abuawwad , Yasmeen Jamal Alabdallat , Abdulqadir J. Nashwan","doi":"10.1016/j.critrevonc.2024.104597","DOIUrl":"10.1016/j.critrevonc.2024.104597","url":null,"abstract":"<div><h3>Background</h3><div>Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.</div></div><div><h3>Objectives</h3><div>This systematic review and meta-analysis aimed to evaluate the safety and efficacy of ibrutinib in the treatment of CNSL, focusing on overall response (OR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events.</div></div><div><h3>Methods</h3><div>A comprehensive search of the PubMed, Google Scholar, and Scopus databases was conducted. The included studies were prospective and retrospective studies focusing on ibrutinib as monotherapy or in combination with CNSL. Data extraction and quality assessment were independently performed by two reviewers, and statistical analyses were conducted using R version 4.4.0.</div></div><div><h3>Results</h3><div>Fourteen studies (eight cohort studies and six clinical trials) involving 784 patients were included. The median age was 61 years, with nearly equal sex distribution. The meta-analysis for CNSL, the partial response rate was 29.52 %, complete response rate was 49.19 %, and overall response rate was 72.11 %. For PCNSL, the partial response rate was 20.85 %, complete response rate was 48.13 %, and overall response rate was 66.92 %. For SCNSL, the partial response rate was 29.42 %, complete response rate was 44.64 %, and overall response rate was 66.82 %. Significant heterogeneity was observed in some comparisons. There were no significant differences in the efficacy of ibrutinib between CNSL subtypes.</div></div><div><h3>Conclusions</h3><div>Ibrutinib shows promising efficacy in improving partial and complete response rates in CNSL. The substantial heterogeneity observed underscores the need for further well-designed studies to confirm these findings and explore the optimal use of ibrutinib in CNSL treatment protocols. Future trials should consider comparing ibrutinib to standard therapies and investigate its long-term efficacy and safety profile.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104597"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104586
Pengfei Ji , Tingting Chen , Chao Li , Jinyuan Zhang , Xiao Li , Hong Zhu
Targeted therapy, the milestone in the development of human medicine, originated in 2004 when the FDA approved the first targeted agent bevacizumab for colorectal cancer treatment. This new development has resulted from drug developers moving beyond traditional chemotherapy, and several trials have popped up in the last two decades with an unprecedented speed. Specifically, EGF/EGFR, VEGF/VEGFR, HGF/c-MET, and Claudin 18.2 therapeutic targets have been developed in recent years. Some targets previously thought to be undruggable are now being newly explored, such as the RAS site. However, the efficacy of targeted therapy is extremely variable, especially with the emergence of new drugs and the innovative use of traditional targets for other tumors in recent years. Accordingly, this review provides an overview of the major signaling pathway mechanisms and recent advances in targeted therapy for gastrointestinal cancers, as well as future perspectives.
{"title":"Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers","authors":"Pengfei Ji , Tingting Chen , Chao Li , Jinyuan Zhang , Xiao Li , Hong Zhu","doi":"10.1016/j.critrevonc.2024.104586","DOIUrl":"10.1016/j.critrevonc.2024.104586","url":null,"abstract":"<div><div>Targeted therapy, the milestone in the development of human medicine, originated in 2004 when the FDA approved the first targeted agent bevacizumab for colorectal cancer treatment. This new development has resulted from drug developers moving beyond traditional chemotherapy, and several trials have popped up in the last two decades with an unprecedented speed. Specifically, EGF/EGFR, VEGF/VEGFR, HGF/c-MET, and Claudin 18.2 therapeutic targets have been developed in recent years. Some targets previously thought to be undruggable are now being newly explored, such as the RAS site. However, the efficacy of targeted therapy is extremely variable, especially with the emergence of new drugs and the innovative use of traditional targets for other tumors in recent years. Accordingly, this review provides an overview of the major signaling pathway mechanisms and recent advances in targeted therapy for gastrointestinal cancers, as well as future perspectives.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104586"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104591
Xiaoan Feng, Guohui Li, Chunyu Li
Immunotherapy has emerged as a powerful tool in cancer treatment, achieving remarkable success in combating various cancers. However, it also raises concerns due to its potential adverse effects, with immune-associated pneumonia being one of the most significant. The clinical symptoms of this condition primarily include dyspnea, persistent cough, and fever. Diagnosis requires knowledge of the patient’s medication history and diagnostic tools like chest CT and bronchoalveolar lavage bronchoscopy to differentiate immune-associated pneumonia from other lung diseases. Studies suggest that the pathogenesis of CIP involves an immune response characterized by overexpression of T-lymphocyte subsets and elevated levels of inflammatory factors. The prevalence of CIP generally ranges between 2 % and 6 %, though it can vary depending on factors like the patient’s individual characteristics, tumor type, and treatment strategy. Corticosteroids are the first-line treatment for CIP, with dosage adjustments based on clinical response. Additionally, traditional Chinese medicine is being explored as an adjuvant therapy to potentially enhance therapeutic outcomes.
{"title":"Recent advances in the study of immune checkpoint inhibitor-associated pneumonia","authors":"Xiaoan Feng, Guohui Li, Chunyu Li","doi":"10.1016/j.critrevonc.2024.104591","DOIUrl":"10.1016/j.critrevonc.2024.104591","url":null,"abstract":"<div><div>Immunotherapy has emerged as a powerful tool in cancer treatment, achieving remarkable success in combating various cancers. However, it also raises concerns due to its potential adverse effects, with immune-associated pneumonia being one of the most significant. The clinical symptoms of this condition primarily include dyspnea, persistent cough, and fever. Diagnosis requires knowledge of the patient’s medication history and diagnostic tools like chest CT and bronchoalveolar lavage bronchoscopy to differentiate immune-associated pneumonia from other lung diseases. Studies suggest that the pathogenesis of CIP involves an immune response characterized by overexpression of T-lymphocyte subsets and elevated levels of inflammatory factors. The prevalence of CIP generally ranges between 2 % and 6 %, though it can vary depending on factors like the patient’s individual characteristics, tumor type, and treatment strategy. Corticosteroids are the first-line treatment for CIP, with dosage adjustments based on clinical response. Additionally, traditional Chinese medicine is being explored as an adjuvant therapy to potentially enhance therapeutic outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104591"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104599
Ying Zhang , Zikun Huang , Weiqing Lu , Zhaoyong Liu
Alternative polyadenylation (APA) serves as a crucial mechanism for the posttranscriptional regulation of gene expression and influences gene expression by generating diverse mRNA isoforms. This process is regulated by a diverse array of RNA-binding proteins (RBPs), which selectively bind to specific sequences or structures within the pre-mRNA molecule. Dysregulation of APA and its associated RBPs has been implicated in numerous diseases, including cardiovascular diseases, nervous system disease, and cancer. For instance, aberrant APA events have been observed in several types of tumors, contributing to tumor heterogeneity and affecting key cellular pathways involved in cell proliferation, invasion, metastasis, and response to therapy. This review critically evaluates the current understanding of APA mechanisms and the multifaceted roles of RBPs in orchestrating this intricate process. We highlight recent advancements in high-throughput sequencing and bioinformatics tools that have enhanced our ability to study APA on a genome-wide scale. Moreover, we explored the pathological consequences of APA dysregulation, emphasizing its role in oncogenesis. By elucidating the intricate relationships between APA and RBPs, this review aims to underscore the potential of targeting the APA machinery and RBPs for therapeutic intervention. Understanding these molecular processes holds promise for developing novel diagnostic markers and treatment strategies for a range of human cancers.
{"title":"Alternative polyadenylation in cancer: Molecular mechanisms and clinical application","authors":"Ying Zhang , Zikun Huang , Weiqing Lu , Zhaoyong Liu","doi":"10.1016/j.critrevonc.2024.104599","DOIUrl":"10.1016/j.critrevonc.2024.104599","url":null,"abstract":"<div><div>Alternative polyadenylation (APA) serves as a crucial mechanism for the posttranscriptional regulation of gene expression and influences gene expression by generating diverse mRNA isoforms. This process is regulated by a diverse array of RNA-binding proteins (RBPs), which selectively bind to specific sequences or structures within the pre-mRNA molecule. Dysregulation of APA and its associated RBPs has been implicated in numerous diseases, including cardiovascular diseases, nervous system disease, and cancer. For instance, aberrant APA events have been observed in several types of tumors, contributing to tumor heterogeneity and affecting key cellular pathways involved in cell proliferation, invasion, metastasis, and response to therapy. This review critically evaluates the current understanding of APA mechanisms and the multifaceted roles of RBPs in orchestrating this intricate process. We highlight recent advancements in high-throughput sequencing and bioinformatics tools that have enhanced our ability to study APA on a genome-wide scale. Moreover, we explored the pathological consequences of APA dysregulation, emphasizing its role in oncogenesis. By elucidating the intricate relationships between APA and RBPs, this review aims to underscore the potential of targeting the APA machinery and RBPs for therapeutic intervention. Understanding these molecular processes holds promise for developing novel diagnostic markers and treatment strategies for a range of human cancers.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104599"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2025.104644
Ashiq Ali , Khadija Younas , Aisha Khatoon , Bilal Murtaza , Ziyi Ji , Kaynaat Akbar , Qaisar Tanveer , Sami Ullah Khan Bahadur , Zhongjing Su
Tissue-resident lymphocytes play a crucial role in immune surveillance against cancer, yet their complex interactions and regulatory pathways remain underexplored, highlighting the need for a deeper understanding to enhance cancer immunotherapy strategies. Lymphocytes across the range of innate-adaptive responses can establish long-lasting presence in tissues, exerting a vital function in the local immune response against diverse antigens. These tissue-resident lymphocytes identify antigens and alarmins secreted by microbial infections and non-infectious stresses at barrier locations by closely interacting with epithelial and endothelial cells. Then they initiate effector responses to restore tissue homeostasis. Significantly, this immune defense system has been demonstrated to monitor the processes of epithelial cell transformation, carcinoma advancement, and cancer metastasis at remote locations, so establishing it as an essential element of cancer immunological surveillance. This review aims to elucidate the roles of diverse tissue-resident lymphocyte populations in shaping cancer immune responses and to investigate their synergistic effector mechanisms for advancing cancer immunotherapy.
{"title":"Immune watchdogs: Tissue-resident lymphocytes as key players in cancer defense","authors":"Ashiq Ali , Khadija Younas , Aisha Khatoon , Bilal Murtaza , Ziyi Ji , Kaynaat Akbar , Qaisar Tanveer , Sami Ullah Khan Bahadur , Zhongjing Su","doi":"10.1016/j.critrevonc.2025.104644","DOIUrl":"10.1016/j.critrevonc.2025.104644","url":null,"abstract":"<div><div>Tissue-resident lymphocytes play a crucial role in immune surveillance against cancer, yet their complex interactions and regulatory pathways remain underexplored, highlighting the need for a deeper understanding to enhance cancer immunotherapy strategies. Lymphocytes across the range of innate-adaptive responses can establish long-lasting presence in tissues, exerting a vital function in the local immune response against diverse antigens. These tissue-resident lymphocytes identify antigens and alarmins secreted by microbial infections and non-infectious stresses at barrier locations by closely interacting with epithelial and endothelial cells. Then they initiate effector responses to restore tissue homeostasis. Significantly, this immune defense system has been demonstrated to monitor the processes of epithelial cell transformation, carcinoma advancement, and cancer metastasis at remote locations, so establishing it as an essential element of cancer immunological surveillance. This review aims to elucidate the roles of diverse tissue-resident lymphocyte populations in shaping cancer immune responses and to investigate their synergistic effector mechanisms for advancing cancer immunotherapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104644"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2025.104645
Yuchao Dan , Xinyi Zhao , Jing Li , Hao Zhong, Haohan Zhang, Jie Wu, Junju He, Lan Li, Qibin Song, Bin Xu
Pseudogenes are abundantly present in the human genome and are often thought of as nonfunctional nucleotide sequences, but a growing body of research suggests that pseudogenes can play important biological roles through a variety of pathways, and can be involved in the development of cancer. Lung cancer is one of the most prevalent cancers in the world and it is crucial to find new therapeutic strategies for the treatment of lung cancer. In recent years, studies on the effects of pseudogenes on lung carcinogenesis have increased rapidly. This has pointed to new directions in the diagnosis and treatment of lung cancer. Aim of this paper is to comprehensively discuss the role and influence of pseudogenes in the lung cancer, and the potential of pseudogenes as novel epigenetic targets in lung cancer diagnosis and prognosis and treatment, which is significant for realizing the clinical benefits of pseudogenes.
{"title":"Harnessing pseudogenes for lung cancer: A novel epigenetic target in diagnosis, prognosis and treatment","authors":"Yuchao Dan , Xinyi Zhao , Jing Li , Hao Zhong, Haohan Zhang, Jie Wu, Junju He, Lan Li, Qibin Song, Bin Xu","doi":"10.1016/j.critrevonc.2025.104645","DOIUrl":"10.1016/j.critrevonc.2025.104645","url":null,"abstract":"<div><div>Pseudogenes are abundantly present in the human genome and are often thought of as nonfunctional nucleotide sequences, but a growing body of research suggests that pseudogenes can play important biological roles through a variety of pathways, and can be involved in the development of cancer. Lung cancer is one of the most prevalent cancers in the world and it is crucial to find new therapeutic strategies for the treatment of lung cancer. In recent years, studies on the effects of pseudogenes on lung carcinogenesis have increased rapidly. This has pointed to new directions in the diagnosis and treatment of lung cancer. Aim of this paper is to comprehensively discuss the role and influence of pseudogenes in the lung cancer, and the potential of pseudogenes as novel epigenetic targets in lung cancer diagnosis and prognosis and treatment, which is significant for realizing the clinical benefits of pseudogenes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104645"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104555
Mansoor Raza Mirza , Domenica Lorusso , Qin Shen , Odette Allonby , Mahmoud Slim , Katarzyna Borkowska , Marissa Betts , Robert L. Coleman
Novel therapies are driving meaningful changes to the management of endometrial cancer (EC). Herein, a systematic literature review was conducted to evaluate the efficacy and safety of first-line treatments for advanced/recurrent EC. Searches were conducted using multiple databases through October 26, 2023. In total, 108 records of 57 unique trials (48 of first-line therapies) met the inclusion criteria. Baseline characteristics varied by study, and sample sizes ranged from 28 to 1328. Median progression-free survival was reported in 28 trials (range, 1.9–18.8 months), median overall survival in 26 trials with mature data (range, 6.9–41 months), and safety in 21 trials evaluating first-line systemic therapy ± maintenance. The potentially high risk of adverse events may outweigh the suboptimal efficacy benefits reported for conventional chemotherapy or hormonal therapies. The safety and efficacy of immunotherapies identified within are expected to contribute to a paradigm shift in the management of primary advanced/recurrent EC.
{"title":"First-line treatments for advanced or recurrent endometrial cancer: Systematic literature review of clinical evidence","authors":"Mansoor Raza Mirza , Domenica Lorusso , Qin Shen , Odette Allonby , Mahmoud Slim , Katarzyna Borkowska , Marissa Betts , Robert L. Coleman","doi":"10.1016/j.critrevonc.2024.104555","DOIUrl":"10.1016/j.critrevonc.2024.104555","url":null,"abstract":"<div><div>Novel therapies are driving meaningful changes to the management of endometrial cancer (EC). Herein, a systematic literature review was conducted to evaluate the efficacy and safety of first-line treatments for advanced/recurrent EC. Searches were conducted using multiple databases through October 26, 2023. In total, 108 records of 57 unique trials (48 of first-line therapies) met the inclusion criteria. Baseline characteristics varied by study, and sample sizes ranged from 28 to 1328. Median progression-free survival was reported in 28 trials (range, 1.9–18.8 months), median overall survival in 26 trials with mature data (range, 6.9–41 months), and safety in 21 trials evaluating first-line systemic therapy ± maintenance. The potentially high risk of adverse events may outweigh the suboptimal efficacy benefits reported for conventional chemotherapy or hormonal therapies. The safety and efficacy of immunotherapies identified within are expected to contribute to a paradigm shift in the management of primary advanced/recurrent EC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104555"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104596
Tiffany M. Juarez , Jaya M. Gill , Boris R. Minev , Akanksha Sharma , Santosh Kesari
Background
High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma.
Methods
A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered.
Results
From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2737 patients.
Conclusion
Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.
背景：高级别胶质瘤是一种毁灭性癌症，标准的手术切除和放化疗仍无法治愈。辐射虽然对肿瘤有益，但会降低淋巴细胞数量，削弱免疫激活，并招募抑制性髓系细胞，损害免疫反应。接受放射治疗的肿瘤环境会经历长期的免疫抑制，从而降低免疫治疗的效果并导致复发。对新诊断患者进行放疗前治疗的调查可以确定活性药物，评估免疫疗法的影响，并在没有辐射引起的混杂因素的情况下进行多组学分析。本文献综述旨在描述针对新诊断高级别胶质瘤成人患者的手术后、放疗前临床试验的可行性、安全性和结果：方法：我们对报道新诊断高级别胶质瘤患者在放疗前接受手术后治疗的临床试验结果的英文文献进行了系统性综述。在PubMed上进行了搜索，同时还考虑了研究和综述文章中引用的参考文献：结果：从 1991 年到 2024 年，共发现了 52 项临床试验：结果：从 1991 年到 2024 年，共发现 52 项临床试验：3 项 I 期、38 项 II 期、4 项 III 期和 7 项未知期。其中9项为随机试验，24项为多中心试验，21项研究了含替莫唑胺的治疗方案，12项主要针对无法手术的肿瘤，共涉及2737名患者：结论：放疗前新辅助治疗研究是可行的，而且可以发现活性药物。结论：放疗前新辅助治疗研究是可行的，而且可以发现有活性的药物。在个性化医疗时代，脑穿刺药物、靶向治疗和免疫肿瘤学的发展尤为重要。在免疫系统和肿瘤微环境保持不变的情况下，对新确诊的高级别胶质瘤进行放疗前治疗研究是快速确定活性和非活性方案的可行方法。
{"title":"Neoadjuvant clinical trials in adults with newly diagnosed high-grade glioma: A systematic review","authors":"Tiffany M. Juarez , Jaya M. Gill , Boris R. Minev , Akanksha Sharma , Santosh Kesari","doi":"10.1016/j.critrevonc.2024.104596","DOIUrl":"10.1016/j.critrevonc.2024.104596","url":null,"abstract":"<div><h3>Background</h3><div>High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma.</div></div><div><h3>Methods</h3><div>A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered.</div></div><div><h3>Results</h3><div>From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2737 patients.</div></div><div><h3>Conclusion</h3><div>Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104596"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2025.104648
David A. Martínez-Gamboa , Rhea Hans , Eider Moreno-Cortes , Juana Figueroa-Aguirre , Juan Esteban Garcia-Robledo , Fabio Vargas-Cely , Natalie Booth , Daniela A. Castro-Martinez , Roberta H. Adams , Januario E. Castro
<div><div>Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative approach in cancer treatment, particularly for hematologic malignancies. This therapy involves the genetic modification of patients' T-cells to target specific tumor antigens, bypassing the traditional MHC-TCR-mediated recognition. This innovation marks a significant step toward personalized medicine and precision oncology. In the pediatric, adolescent, and young adult (P-AYA) populations, Tisagenlecleucel (Kymriah®) exemplifies the success of CAR T-cell therapy, demonstrating significant efficacy in treating relapsed or refractory acute lymphoblastic leukemia (r/r ALL). However, the development of CAR T-cell therapies for P-AYA patients has not progressed as rapidly as for adults, with only one FDA approval for pediatric applications compared to six for adults up to 2024. Several challenges hinder the development of pediatric CAR T-cell therapies, including complex production logistics, limited clinical site access, restrictive patient eligibility criteria, and financial constraints, necessitating more effective incentives for pediatric oncology drug development independent of adult indications. To assess the current landscape of CAR T-cell therapy in P-AYA oncology, we conducted a comprehensive review of clinical trials registered on ClinicalTrials.gov up to May 2024. Our analysis included 77 trials exclusively targeting the P-AYA population from an initial pool of 40,690 studies filtered by age, dates, and specific criteria related to CAR T-cell interventions in cancer therapy. We found that 45 % of these trials originated from the USA and 30 % from China. The data retrieved from these trials provided insights into various aspects, including histological categories, antigenic targets, CAR-T generations, costimulatory domains, manufacturing processes, geographical distribution, and funding sources. This review highlighted a predominant focus on hematologic malignancies, particularly B-cell acute lymphoblastic leukemia (B-ALL), with significant attention to dual antigen targeting (CD19 and CD22) to address resistance mechanisms. Emerging targets such as GD2 for solid tumors and B7-H3 for various cancers also showed promise. Additionally, most trials still utilize second-generation CAR-T constructs with 4–1BB costimulatory domains, reflecting a conservative approach in pediatric populations. Our findings underscore the disparity in CAR T-cell therapy development between pediatric and adult populations, driven by distinct biological, ethical, and economic considerations. Pediatric cancers require specialized treatments tailored to the unique biology and genetic makeup of pediatric oncology. However, research and drug development have historically focused less on pediatric needs. Despite legislative efforts to promote pediatric oncology drug development, significant gaps remain. Clinical trials for P-AYA populations face challenges in patient enrollment, trial
{"title":"CAR T-cell therapy landscape in pediatric, adolescent and young adult oncology – A comprehensive analysis of clinical trials","authors":"David A. Martínez-Gamboa , Rhea Hans , Eider Moreno-Cortes , Juana Figueroa-Aguirre , Juan Esteban Garcia-Robledo , Fabio Vargas-Cely , Natalie Booth , Daniela A. Castro-Martinez , Roberta H. Adams , Januario E. Castro","doi":"10.1016/j.critrevonc.2025.104648","DOIUrl":"10.1016/j.critrevonc.2025.104648","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative approach in cancer treatment, particularly for hematologic malignancies. This therapy involves the genetic modification of patients' T-cells to target specific tumor antigens, bypassing the traditional MHC-TCR-mediated recognition. This innovation marks a significant step toward personalized medicine and precision oncology. In the pediatric, adolescent, and young adult (P-AYA) populations, Tisagenlecleucel (Kymriah®) exemplifies the success of CAR T-cell therapy, demonstrating significant efficacy in treating relapsed or refractory acute lymphoblastic leukemia (r/r ALL). However, the development of CAR T-cell therapies for P-AYA patients has not progressed as rapidly as for adults, with only one FDA approval for pediatric applications compared to six for adults up to 2024. Several challenges hinder the development of pediatric CAR T-cell therapies, including complex production logistics, limited clinical site access, restrictive patient eligibility criteria, and financial constraints, necessitating more effective incentives for pediatric oncology drug development independent of adult indications. To assess the current landscape of CAR T-cell therapy in P-AYA oncology, we conducted a comprehensive review of clinical trials registered on ClinicalTrials.gov up to May 2024. Our analysis included 77 trials exclusively targeting the P-AYA population from an initial pool of 40,690 studies filtered by age, dates, and specific criteria related to CAR T-cell interventions in cancer therapy. We found that 45 % of these trials originated from the USA and 30 % from China. The data retrieved from these trials provided insights into various aspects, including histological categories, antigenic targets, CAR-T generations, costimulatory domains, manufacturing processes, geographical distribution, and funding sources. This review highlighted a predominant focus on hematologic malignancies, particularly B-cell acute lymphoblastic leukemia (B-ALL), with significant attention to dual antigen targeting (CD19 and CD22) to address resistance mechanisms. Emerging targets such as GD2 for solid tumors and B7-H3 for various cancers also showed promise. Additionally, most trials still utilize second-generation CAR-T constructs with 4–1BB costimulatory domains, reflecting a conservative approach in pediatric populations. Our findings underscore the disparity in CAR T-cell therapy development between pediatric and adult populations, driven by distinct biological, ethical, and economic considerations. Pediatric cancers require specialized treatments tailored to the unique biology and genetic makeup of pediatric oncology. However, research and drug development have historically focused less on pediatric needs. Despite legislative efforts to promote pediatric oncology drug development, significant gaps remain. Clinical trials for P-AYA populations face challenges in patient enrollment, trial ","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104648"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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