Critical reviews in oncology/hematology最新文献

{"title":"Recent development in bispecific antibody immunotherapy for hematological malignancies","authors":"Lijie Han ,&nbsp;Ke Wang ,&nbsp;Zhongxing Jiang ,&nbsp;Xuejun Guo ,&nbsp;Jifeng Yu","doi":"10.1016/j.critrevonc.2025.104752","DOIUrl":"10.1016/j.critrevonc.2025.104752","url":null,"abstract":"<div><div>While monoclonal antibody (mAb)-based therapies have revolutionized cancer treatment, challenges such as resistance mechanisms and tumor progression via alternative pathways underscore the need for novel therapeutic strategies. Bispecific antibodies (BsAbs), which target two distinct antigens simultaneously, represent a promising next-generation solution, improving therapeutic precision, efficacy, and safety. BsAbs also redirect cytotoxic effector cells to tumor sites, providing additional therapeutic mechanisms. Recent advancements in BsAb design, such as enhancements in pharmacokinetics and modular multi-specific formats, are expanding their use in hematological malignancies. Combining BsAbs with immune checkpoint inhibitors and other therapies may overcome resistance and improve clinical outcomes. Leading BsAbs, including mosunetuzumab, glofitamab, and blinatumomab, have demonstrated promising efficacy in clinical trials for leukemia and lymphoma subtypes. Despite remaining challenges, particularly in acute myeloid leukemia (AML), ongoing research into new targets and combination therapies is expected to enhance the efficacy of BsAbs in relapsed or refractory (R/R) disease. This review explores the structural and functional innovations of BsAbs, the challenges in current therapies, and their transformative potential in hematological malignancy immunotherapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104752"},"PeriodicalIF":5.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907085","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}

{"title":"CircRNAs in the tumor microenvironment: new frontiers in cancer progression and therapy","authors":"Yipei Guo ,&nbsp;Yuanxun Gong ,&nbsp;Man Wu ,&nbsp;Mengjia Ji ,&nbsp;Fei Xie ,&nbsp;Hao Chen ,&nbsp;Haitao Niu ,&nbsp;Chao Tang","doi":"10.1016/j.critrevonc.2025.104754","DOIUrl":"10.1016/j.critrevonc.2025.104754","url":null,"abstract":"<div><div>The tumor microenvironment (TME), a dynamic ecosystem which including immune cells, cancer-associated fibroblasts (CAFs), endothelial cells, pericytes and acellular components, is orchestrating cancer progression through crosstalk between malignant cells and stromal components and increasingly recognized as a therapeutic frontier. Within this intricate network, circular RNAs (circRNAs) have emerged as pivotal regulators due to their unique covalently closed structures, which confer exceptional stability and multifunctional capabilities. This regulation is mediated through multiple mechanisms, such as acting as microRNA (miRNA) sponges, interacting with proteins, and, in certain instances, encoding functional peptides. The interaction between circRNAs and the TME not only affects cancer growth and metastasis but also influences immune evasion and therapeutic resistance. Elucidating the mechanisms by which circRNAs orchestrate these interactions is essential for identifying novel diagnostic biomarkers and developing effective therapeutic strategies. Such insights are expected to bridge gaps in current cancer biology, offering promising avenues for precision oncology and ultimately improving clinical outcomes for cancer patients.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104754"},"PeriodicalIF":5.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907086","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}

{"title":"The role and clinical significance of tumor-draining lymph nodes in tumor progression and immunotherapy","authors":"Qian Xu ,&nbsp;Jiahui Chu ,&nbsp;Qinqin Hu ,&nbsp;Yanheng Sun ,&nbsp;Fan Jiang ,&nbsp;Song Li ,&nbsp;Lian Liu","doi":"10.1016/j.critrevonc.2025.104745","DOIUrl":"10.1016/j.critrevonc.2025.104745","url":null,"abstract":"<div><div>Tumor-draining lymph nodes (TDLNs) play a pivotal role in tumor growth and the immune response, activating immune cells such as CD8 + T cells and natural killer cells to combat tumors. However, tumors can subvert TDLNs to avoid immune attack. Initially, TDLNs stimulate a robust antitumor response, but as tumor evolve, they infiltrate with immunosuppressive cells that alter the TDLN environment and potentially promote metastasis. Immunotherapy, including immune checkpoint inhibitor (ICI), have emerged as a potential solution to this challenge by reconfiguring the TDLN environment to enhance immune responses and influence the immune status of the primary tumor. The integrity of the TDLNs is crucial for the efficacy of immunotherapy. Conventional surgery often removes TDLNs, but this may impede immune system function and the effectiveness of immunotherapy. It is therefore recommended that removal of TDLNs be considered after neoadjuvant treatment rather than before adjuvant treatment. Accurate identification of patients who require post-neoadjuvant TDLN removal and the determination of metastatic nodes is of paramount importance in tailoring treatment plans, optimizing of patient outcomes, and improving quality of life.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104745"},"PeriodicalIF":5.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907084","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}

{"title":"Should adjuvant treatments be escalated in node-positive HR+/HER2- patients achieving pCR and omitting axillary dissection?","authors":"Maria Vita Sanò,&nbsp;Lorenza Marino,&nbsp;Giuseppina Rosaria Rita Ricciardi","doi":"10.1016/j.critrevonc.2025.104732","DOIUrl":"10.1016/j.critrevonc.2025.104732","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104732"},"PeriodicalIF":5.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904039","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}

{"title":"Regulation of the CD8⁺ T cell and PDL1/PD1 axis in gastric cancer: Unraveling the molecular landscape","authors":"Xin Yong ,&nbsp;Dong Mu ,&nbsp;Hua Ni,&nbsp;Xue Wang,&nbsp;Tongqin Zhang,&nbsp;Xing Chang,&nbsp;Sheng He,&nbsp;Dejiang Zhou","doi":"10.1016/j.critrevonc.2025.104750","DOIUrl":"10.1016/j.critrevonc.2025.104750","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a significant global health burden, mainly due to immune evasion mechanisms within its complex tumor microenvironment (TME). The interaction between CD8⁺ T cells and the PD1/PDL1 axis is central to these mechanisms. CD8⁺ T cells, key players in antitumor immunity, often exhibit impaired functionality in the GC TME, primarily due to PD1-mediated inhibitory signaling induced by PDL1 expressed on tumor and immune cells. Recent findings have elucidated intricate molecular interactions governing PD1 expression on CD8⁺ T cells and the modulation of PDL1 on tumor cells and immune cells by diverse signals such as cytokines, metabolic factors, and noncoding RNAs. While high PD1 expression typically indicates CD8⁺ T cell exhaustion and poor clinical outcomes, recent studies highlight scenarios where elevated PD1 levels correlate with preserved or enhanced T cell cytotoxic activity, suggesting nuanced regulatory pathways. Therapeutic strategies that disrupt PD1/PDL1 interactions, through checkpoint inhibitors or pharmacological modulation, have demonstrated potential in reactivating antitumor responses. However, resistance mechanisms, including altered antigen presentation, metabolic reprogramming, and immunosuppressive cell infiltration, continue to limit efficacy. Emerging combination therapies, biomarker-driven patient stratification, and novel targets like noncoding RNAs and exosomal PDL1 represent promising avenues to enhance treatment effectiveness. This review synthesizes current insights into the molecular regulation of CD8⁺ T cell functionality and the PD1/PDL1 axis, highlighting potential therapeutic strategies to restore antitumor immunity and improve patient outcomes in gastric cancer.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104750"},"PeriodicalIF":5.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937052","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}

{"title":"Revolutionizing immunotherapy: The next frontier in CAR T-cell engineering","authors":"Anuupama Suchiita ,&nbsp;Subash Chandra Sonkar","doi":"10.1016/j.critrevonc.2025.104751","DOIUrl":"10.1016/j.critrevonc.2025.104751","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking immunotherapy, offering new hope for cancer treatment, particularly in hematologic malignancies. This review explores the development of CAR T-cell therapy from its first-generation design, which laid the foundational structure, to advanced fifth-generation CARs that integrate sophisticated synthetic biology. Each generation of CARs has introduced critical improvements, such as the incorporation of costimulatory domains, dual signaling pathways, and cytokine release mechanisms to enhance T-cell activation, persistence, and efficacy. Current applications of CAR T-cell therapy have seen significant success in treating cancers like acute lymphoblastic leukemia and diffuse large B-cell lymphoma, with several therapies gaining regulatory approval. However, challenges persist in targeting solid tumors due to the immunosuppressive tumor microenvironment and antigen heterogeneity. Ongoing clinical trials and research are focused on overcoming these barriers through next-generation CAR designs, novel antigen targets, and combination therapies. The review highlights recent advancements, emerging targets, and the potential of CAR T-cell therapy to revolutionize cancer treatment, paving the way for more effective and personalized approaches.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"211 ","pages":"Article 104751"},"PeriodicalIF":5.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906607","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}

{"title":"Beneath the surface of colorectal cancer: Unmasking the evolving nature of (Neo)RAS","authors":"Giulia Massaro ,&nbsp;Jacopo Venturini ,&nbsp;Daniele Rossini ,&nbsp;Agnese Vannini ,&nbsp;Marco Brugia ,&nbsp;Daniele Lavacchi ,&nbsp;Cristiana Conticello ,&nbsp;Irene Valle ,&nbsp;Delia Ravizza ,&nbsp;Serena Pillozzi ,&nbsp;Lorenzo Antonuzzo","doi":"10.1016/j.critrevonc.2025.104746","DOIUrl":"10.1016/j.critrevonc.2025.104746","url":null,"abstract":"<div><div>Metastatic colorectal cancer (mCRC) remains a major clinical challenge, despite therapeutic advancements. Mutations in KRAS and NRAS (RAS) oncogenes drive resistance to anti-EGFR drugs, necessitating RAS mutational analysis prior to treatment. While tissue biopsy remains the gold standard for molecular profiling, it has limitations such as invasiveness, intra-tumoral heterogeneity, and delayed results. Liquid biopsy (LB), on the other hand, offers a non-invasive alternative by analyzing circulating tumor DNA (ctDNA) and it provides a dynamic view of molecular changes over time. Indeed, ctDNA analysis has expanded the understanding of the mCRC’s molecular landscape, revealing that RAS mutated (MT) subclones undergo both a positive and a negative selection during treatment. This negative selection has been described as the \"NeoRAS WT phenomenon.\" The temporary disappearance of RAS mutations opens \"RAS WT windows,” thus making potential candidates for anti-EGFR therapies even patients initially diagnosed as RAS MT. This review examines numerous studies investigating the clinical significance of the “NeoRas WT phenomenon” as a distinct pathological entity. It also highlights the key limitations arising from the variability in study designs, detecting methods and ctDNA shedding rates. The results of ongoing prospective trials are necessary to determine whether NeoRAS WT stands as a reliable marker for guiding anti-EGFR treatment strategies in RAS-mutated patients.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"211 ","pages":"Article 104746"},"PeriodicalIF":5.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904580","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}

{"title":"Intrapleural fibrinolytic therapy for loculated malignant pleural effusion: A systematic review and meta-analysis","authors":"Toshiaki Takahashi ,&nbsp;Sharina Macapagal ,&nbsp;Chalothorn Wannaphut ,&nbsp;Yoshito Nishimura","doi":"10.1016/j.critrevonc.2025.104749","DOIUrl":"10.1016/j.critrevonc.2025.104749","url":null,"abstract":"<div><h3>Background</h3><div>Malignant pleural effusion (MPE) is a common complication in advanced malignancies, often presenting with dyspnea and impaired quality of life. Management can be challenging, particularly in cases with loculated effusions or non-expandable lungs. Intrapleural fibrinolytic therapy (IFT) has been proposed as a potential adjunctive treatment, although its efficacy for loculated MPE remains inconclusive</div></div><div><h3>Methods</h3><div>A systematic search was conducted across PubMed and Embase, and a meta-analysis was conducted to assess the efficacy and safety of IFT for MPE. Eligible studies included randomized controlled trials (RCTs) and retrospective studies comparing IFT with control interventions. The primary outcome was respiratory improvement; secondary outcomes included complication rates, treatment failure or clinical recurrence, hemorrhagic complications, and hospital length of stay.</div></div><div><h3>Results</h3><div>Six studies (n = 653) were included, comprising three RCTs and three retrospective cohort studies. IFT was associated with significantly greater respiratory improvement (OR = 5.25, 95 % CI: 3.54–7.80, p &lt; 0.05), with consistent findings in both RCT and retrospective subgroups. There were no statistically significant differences in overall complication rates, treatment failure, hemorrhagic complications, or length of hospital stay. Subgroup analyses revealed a higher complication OR in retrospective studies (OR = 3.36) and a lower OR in RCTs (OR = 0.78), although both were statistically non-significant.</div></div><div><h3>Conclusion</h3><div>IFT is associated with favorable respiratory outcomes in patients with MPE with an acceptable safety profile, suggesting its potential role as an adjunct to standard therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"211 ","pages":"Article 104749"},"PeriodicalIF":5.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906608","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}

{"title":"Clinical trials for patients with salivary gland cancers: A systematic review of worldwide registers and an evaluation of current challenges","authors":"Pablo Jiménez-Labaig ,&nbsp;Luigi Lorini ,&nbsp;Cristina Gurizzan ,&nbsp;Emma Kinloch ,&nbsp;Sarah Burton ,&nbsp;Martin D. Forster ,&nbsp;Robert Metcalf ,&nbsp;Renata Ferrarotto ,&nbsp;Paolo Bossi ,&nbsp;Ben O´leary ,&nbsp;Glenn Hanna ,&nbsp;Enriqueta Felip ,&nbsp;Irene Braña Garcia ,&nbsp;Kevin J. Harrington","doi":"10.1016/j.critrevonc.2025.104747","DOIUrl":"10.1016/j.critrevonc.2025.104747","url":null,"abstract":"<div><h3>Background</h3><div>Clinical trials (CT) are crucial for generating scientific evidence and improving clinical outcomes, but they can be challenging in the context of rare cancers. Salivary gland cancers (SGC) are rare and heterogeneous tumors, without standard-of-care approved systemic therapies. We analyzed completed and ongoing CTs to assess the current state of clinical research activity in the field.</div></div><div><h3>Methods</h3><div>ClinicalTrials.gov, WHO-ICTRP, HealthCanadaCT were searched for antineoplastic pharmacological and interventional CT involving patients with SGC from the trials database creation until August 6th, 2024. CT characteristics and status were collected.</div></div><div><h3>Results</h3><div>134 clinical trials met inclusion criteria. Of these, 78 % were sponsored by non-industry entities. 49 % were conducted at only one site, and 61 % at up to five centers. Only 25 trials (19 %) were multinational, being 15 industry-sponsored, a significantly higher proportion compared to non-industry-sponsored trials(p &lt; 0.01). 16 % CTs were umbrella or basket, and 6 % were randomized, again predominantly industry-sponsored(p &lt; 0.01). Regarding SGC-specific trials, 32 % were open to all patients with SGC, regardless of specific histology. Patients with adenoid cystic, salivary duct, and mucoepidermoid carcinoma had access to 92 %, 66 % and 62 % of trials, respectively. 88 % CT targeted palliative setting, and 38 % incorporated predictive biomarkers. Tyrosine kinase inhibitors were the most studied therapy(26 %), followed by immunotherapy(15 %), chemotherapy and antibody-drug conjugate(12 % each) and androgen-blockade(8 %), among others.</div></div><div><h3>Conclusion</h3><div>Clinical research for patients with SGC relies mainly in non-industry organisations, most of them limited to run trials in one to five sites, in a single country. Further collaboration between investigators is needed, as well as reconsidering inclusion criteria and trial designs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"211 ","pages":"Article 104747"},"PeriodicalIF":5.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891152","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}

{"title":"Extracellular vesicles in acute myeloid leukemia: The role in disease pathogenesis, potential biomarker, and application in clinical settings","authors":"Madhura Chatterjee ,&nbsp;Saurabh Gupta ,&nbsp;Umesh Kumar ,&nbsp;Deepak Parashar ,&nbsp;Arindam Maitra ,&nbsp;Kaushik Das","doi":"10.1016/j.critrevonc.2025.104743","DOIUrl":"10.1016/j.critrevonc.2025.104743","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML), the most prevalent type of blood cancer, is initiated in the bone marrow and eventually migrates into the blood. It accounts for a 5-year overall survival rate of 29.8 %. AML results from the formation of immature white blood cells, also called AML blasts, from hematopoietic stem cells which eventually give rise to abnormal white blood cells, termed AML cells. The interaction of AML cells with their microenvironment appears to be significantly important in the pathogenesis of AML. A growing body of evidence identifies extracellular vesicles (EVs) to be a key component in intercellular communication via the transfer of biomolecules, such as DNA, RNAs, proteins, non-coding RNAs, lipids, metabolites etc. Although the role of EVs in various solid tumors is well-established, EVs’ contribution to the pathogenesis of blood cancer, such as AML remains ill-defined. The present review highlights how EVs promote the progression of AML by influencing leukemogenesis, survival, angiogenesis, chemotherapeutic resistance, and immune evasion. A significant number of EVs are found in the biofluids of AML patients which are shown to carry signature cargo molecules, thereby rendering the EVs as predictive biomarkers for AML pathogenesis. EV-based clinical trials are mentioned in the later part of the review. Finally, EV-based therapeutics and their limitations are also briefly discussed in the context of AML.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"211 ","pages":"Article 104743"},"PeriodicalIF":5.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881857","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}