Critical reviews in oncology/hematology最新文献

{"title":"Anticancer mechanisms and applications based on γδ T cells in cancer immunotherapy","authors":"Qun Yang ,&nbsp;Jintong Na ,&nbsp;Simin Qin ,&nbsp;Jingyi Su ,&nbsp;Honghua Huang ,&nbsp;Liping Zhong","doi":"10.1016/j.critrevonc.2025.104814","DOIUrl":"10.1016/j.critrevonc.2025.104814","url":null,"abstract":"<div><div>Cancer continues to be a major global health challenge, posing a substantial threat to human well-being, with a high mortality rate. Although recent advancements have significantly enhanced the effectiveness of cancer treatment, the percentage of metastasis and recurrence remains high. Immunotherapy has emerged as a potent cancer treatment method with high specificity and limited or manageable side effects; thus, it has garnered considerable attention. Among the promising candidates for the next generation of tumor immunotherapy are γδ T cells, which are effector lymphocytes and a subpopulation of T cells characterized by receptors composed of γ and δ chains, and are a unique cell type that mediates between intrinsic and specific immunity. Additionally, γδ T cells are capable of secreting a variety of cytokines, playing a crucial role in both multiple homeostatic and disease-associated processes <em>in vivo</em>, and perform a significant function in immune surveillance and defense. Unlike αβ T cells, γδ T cells possess an antigen-specific recognition capability that is neither restricted by the major histocompatibility complex (MHC) nor dependent on antigen-presenting cells. Both foundational research and clinical studies have demonstrated that γδ T cells derived from peripheral blood or tumor tissues and expanded using nitrogen-containing phosphates and interleukin (IL)-2 exhibit cytotoxic effects against various tumor types. Therefore, to achieve a thorough and comprehensive understanding of the practical applications and functional mechanisms of γδ T cells in oncology, we present a review of advancements in research on γδ T cell immunology and its application and mechanism in cancer treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104814"},"PeriodicalIF":5.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369710","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":"Trimodal treatment vs radical cystectomy for muscle-invasive bladder cancer: The neglected impact of informative censoring. A systematic review and meta-analysis","authors":"Daniele Robesti ,&nbsp;Filippo Micheli ,&nbsp;Shesh N. Rai ,&nbsp;Giuseppe Fallara ,&nbsp;Andrea Gallina ,&nbsp;Francesco Montorsi ,&nbsp;Alberto Briganti ,&nbsp;Nicola Fossati ,&nbsp;Antoine G. van der Heijden ,&nbsp;Guillaume Ploussard ,&nbsp;Bernard Malavaud ,&nbsp;Alberto Martini","doi":"10.1016/j.critrevonc.2025.104815","DOIUrl":"10.1016/j.critrevonc.2025.104815","url":null,"abstract":"<div><h3>Introduction</h3><div>Informative censoring (IC) is a statistical bias that occurs when there is an imbalance in the dropout rate among study arms and this imbalance is not random, but can be ascribed to information that is not accounted for. Studies on trimodal therapy (TMT) versus radical cystectomy (RC) yielded conflicting results. We conducted a meta-analysis to assess the potential impact of informative censoring in influencing study outcomes.</div></div><div><h3>Materials and methods</h3><div>A systematic literature search identified studies involving patients with cT2–4 any N, M0 muscle-invasive bladder cancer treated with TMT versus RC to assess the risk of informative censoring in assessing oncological measures. We reconstructed published Kaplan-Meier curves to obtain time-to-event data and applied the inverse Kaplan-Meier method alongside the log-rank test to evaluate the presence of informative censoring. Finally, we performed a simulation analysis to assess the minimum proportion of events required among censored patients to compensate for the potential effect of IC.</div></div><div><h3>Results</h3><div>Overall, 6 studies with 8594 patients were included; 4 used propensity score matching, while 2 did not. An imbalance in censoring was present in 10 of 12 reported outcomes, with bias favoring RC in 5 instances and TMT in 5 instances. Overall, censoring favored RC in overall survival (OS), metastasis-free survival, and disease-free survival (Log-rank: all <em>p</em> &lt; 0.01). These findings were consistent after stratifying for propensity score matching and neoadjuvant chemotherapy. For OS, the minimum proportion of events required compensate for the potential effect of IC ranged from 16 % to 33 %. After adjusting for potential presence of IC, RC was still superior in terms of OS relative to TMT (5-year OS: 42 % vs. 30 %; <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Most retrospective studies comparing TMT to RC are at high risk of informative censoring. IC tends to favor radical cystectomy. After correcting for IC, the oncological outcomes of patients undergoing RC were still superior to the ones who undergo TMT. Our data underline the complexity of comparing oncological outcomes between TMT and RC, and challenge the acceptance of TMT based on retrospective comparison in spite of randomization.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104815"},"PeriodicalIF":5.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365010","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":"Predictive performance of the clinicopathologic gene expression profile (CP-GEP) in identifying cutaneous melanoma patients for whom sentinel lymph node biopsy is unnecessary: A systematic review and meta-analysis","authors":"Terence Wong ,&nbsp;Sydney Ch’ng ,&nbsp;Peter Ferguson ,&nbsp;Linda Martin ,&nbsp;Alexander M. Menzies ,&nbsp;Inês Pires da Silva ,&nbsp;Georgina V. Long ,&nbsp;Richard A. Scolyer ,&nbsp;Alexander van Akkooi ,&nbsp;Serigne N. Lo","doi":"10.1016/j.critrevonc.2025.104816","DOIUrl":"10.1016/j.critrevonc.2025.104816","url":null,"abstract":"<div><h3>Context &amp; aim</h3><div>Sentinel lymph node biopsy (SLNB) is an invasive procedure that detects microscopic nodal metastasis, crucial for accurate staging and optimal management. In melanoma, most patients who undergo the procedure have no sentinel lymph node (SLN) metastasis detected. The CP-GEP model (Merlin Assay) was developed to identify patients who do not have SLN metastases and who may therefore safely forgo SLNB, based upon clinicopathologic and gene expression features of the primary tumour. While the Merlin Assay has been validated by independent cohorts with relatively moderate sample sizes, this meta-analysis aims to assess the overall predictive performance of the model and examine potential heterogeneity between the external validation cohorts.</div></div><div><h3>Method</h3><div>We conducted a literature search in MEDLINE and Embase for studies that externally validated the CP-GEP model and were published between January 2019 and June 2024. Studies that reported the model’s sensitivity and specificity were included. Quality assessment was conducted by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The outcomes investigated were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and SLNB reduction rate, defined as the proportion of patients that can forgo SLNB based on the Merlin Assay outcome. Individual estimates were pooled using random effects meta-analysis model. Subgroup analysis was performed by T category.</div></div><div><h3>Findings (Impact)</h3><div>Four external validation studies (three retrospective and one prospective) were identified and included, involving 1099 participants. The pooled median age was 60 years and median Breslow thickness was 1.8 mm. Across all primary tumour classification groups (pT1-pT4), the pooled sensitivity was 93 % (95 % CI: 88 %-96 %), specificity was 32 % (95 % CI: 23 %-41 %), PPV was 24 % (95 % CI: 18 %-31 %), NPV was 95 %, (95 % CI: 92 %-97 %) and SLNB reduction rate was 27 % (95 % CI: 20 %-35). The subgroup analysis revealed that the model performed best in the pT2 group; pooled sensitivity was 91 % (95 % CI: 82 %-96 %), specificity was 35 % (95 % CI: 30 %-39 %), PPV was 20 % (95 % CI: 14 %-27 %), NPV was 96 %, (95 % CI: 91 %-98 %) and SLNB reduction rate was 31 % (95 % CI: 27 %-35 %).</div></div><div><h3>Conclusion</h3><div>This meta-analysis suggests that the CP-GEP model can reduce the number of unnecessary SLNBs performed, especially in pT2 patients. It can improve clinical decision making and assist in patients’ informed consent. Broader implications such as potential reductions in healthcare costs and risks of surgical complications should be explored further.</div></div><div><h3>PROSPERO registration</h3><div>CRD42024547893</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104816"},"PeriodicalIF":5.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369711","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":"Targeting the DNA damage response to enhance radiotherapy in soft tissue sarcomas","authors":"Bauke H.G. van Riet ,&nbsp;Sanne Venneker ,&nbsp;Judith V.M.G. Bovée ,&nbsp;Neeltje Steeghs ,&nbsp;Rick L. Haas","doi":"10.1016/j.critrevonc.2025.104811","DOIUrl":"10.1016/j.critrevonc.2025.104811","url":null,"abstract":"<div><div>Radiotherapy plays an important role in treating non-metastatic soft tissue sarcomas by inducing DNA damage and subsequent cell death. However, all cells possess defence mechanisms to repair DNA damage via DNA damage response (DDR) pathways. Inhibition of these DDR pathways may enhance tumour sensitivity to radiation, potentially improving treatment outcomes. This review assesses the potential of DDR inhibition to enhance radiosensitivity in soft tissue sarcomas, by evaluating both preclinical and clinical studies that combined DDR inhibitors and radiotherapy. Studies were identified by searching literature databases, clinical trial registries and conference abstracts, and focused on the relevance for combining DDR inhibitors and radiotherapy in soft tissue sarcoma treatment. Targeting DDR pathways through key proteins like PARP, ATM and ATR appears to be a promising approach to increase the radiosensitivity of soft tissue sarcomas in preclinical studies with minimal increased toxicity. Although phase I and II clinical trials observed that DDR inhibitors are mostly well tolerated, phase II trials observed limited to no improvement in disease control or overall survival. Moreover, some trials observed increased severe toxicities, especially at higher radiation doses or accelerated schedules. Nevertheless, DDR inhibitors have a great potential to sensitize soft tissue sarcomas to radiotherapy. Unfortunately, the currently developed DDR inhibitors have shown limited effect on overall survival and recurrence rates. Therefore, efforts should be made to either improve their efficacy or to reduce radiation doses through DDR inhibitor-mediated radiosensitization while maintaining efficacy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104811"},"PeriodicalIF":5.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331266","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 effects of race on anti-PD-(L)1 monoclonal antibodies in non-small cell lung cancer: A systematic literature review and meta-analysis","authors":"Carlo Genova ,&nbsp;Federico Cappuzzo ,&nbsp;Giorgio Minotti ,&nbsp;Nicola Normanno ,&nbsp;Barry Rodgers-Gray ,&nbsp;Nicola Waghorne ,&nbsp;Silvia Novello ,&nbsp;Marcello Tiseo","doi":"10.1016/j.critrevonc.2025.104812","DOIUrl":"10.1016/j.critrevonc.2025.104812","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) represents approximately 85 % of lung cancers, with five-year survival only 4.5 % for metastatic disease. Programmed death (ligand)-1 (PD-[L]1) inhibitors have advanced NSCLC treatment, but patient demographics can potentially affect clinical outcomes. This systematic literature review and meta-analysis were undertaken to determine if the benefits of anti-PD-(L)1 therapies in NSCLC are independent of race (bio-geographic background).</div></div><div><h3>Methods</h3><div>PubMed, Embase, Cochrane Library and World Health Organization Global Index Medicus were systematically searched (inception-to-Aug-2024). Primary analysis focused on studies with subgroup analysis (White vs Asian, White vs Non-White, Asian vs Non-Asian) of anti-PD-(L)1 efficacy in both resectable/localized and unresectable/advanced NSCLC. Subgroup analysis included stratification by PD-L1 expression, treatment line, and treatment regimen. Bayesian inferential meta-analysis was performed for outcomes with ≥ 1 study.</div></div><div><h3>Results</h3><div>From 4406 records, 22 randomized controlled trials, 3 pooled analyses, and 2 pharmacokinetic studies were included. In unresectable/advanced NSCLC, anti-PD-(L)1 therapy significantly improved overall survival and progression-free survival (PFS) for White (hazard ratio [HR] 0.80; 95 % credible interval [95 % CrI] 0.74–0.87, p &lt; 0.001 and HR 0.68; 95 % CrI 0.61–0.77, p &lt; 0.001, respectively) and Asian (HR 0.81; 95 % CrI 0.69–0.96, p = 0.027 and HR 0.63; 95 % CrI 0.50–0.80, p = 0.002) patients. The significant improvements in PFS were maintained for both groups within all sub-analyses. Limited data prohibited conduction of meta-analysis for resectable/localized NSCLC.</div></div><div><h3>Conclusions</h3><div>The benefits of anti-PD-(L)1 therapy in unresectable/advanced NSCLC appear similar for White and Asian patients. Increased quality and quantity of data is required to draw definitive conclusions for resectable/localized NSCLC and with respect to treatment line/regimen and PD-L1 expression.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104812"},"PeriodicalIF":5.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337358","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 molecules with double-edged sword roles in T cell: An implication for adoptive T cell therapy","authors":"Marziyeh Samiee,&nbsp;Saeedeh Salehi,&nbsp;Leila Mohamed Khosroshahi,&nbsp;Tahereh Soltantoyeh","doi":"10.1016/j.critrevonc.2025.104810","DOIUrl":"10.1016/j.critrevonc.2025.104810","url":null,"abstract":"<div><div>Immune checkpoints have traditionally been viewed as inhibitory molecules that downregulate immune cell activity, acting as a safeguard against excessive immune responses. In chronic infections and cancer, however, these checkpoints serve as barriers that can inhibit effective immune responses, thereby reducing pathological consequences. Over the years, researchers have explored immune checkpoint blockade through antibody-based therapies and have sought to delete these molecules in adoptive T cell therapy to enhance T cell function and proliferation. However, emerging research suggests that immune checkpoint deletion may not always be advantageous; these molecules appear to play complex roles in supporting T cell functions like metabolism, cytotoxicity, proliferation and persistence. Some of them might have roles in T cell differentiation into subsets like memory cells. This article delves into the evolving understanding of immune checkpoint molecules, such as PD-1, TIM-2, A2aR, 2B4 and EP2, highlighting their nuanced roles in immune regulation and implications for immunotherapy. We proposed that these molecules should be viewed as a double-edged sword and regulated with greater caution, taking into account their lesser-known roles and other interacting factors.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104810"},"PeriodicalIF":5.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487450","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":"Dual roles of GM-CSF in breast cancer: Immunomodulation and therapeutic implications","authors":"Yuxuan Guo ,&nbsp;Yingya Hu ,&nbsp;Da Huang ,&nbsp;Jiangnan Yang ,&nbsp;Shujun Fu ,&nbsp;Xiyun Deng ,&nbsp;Jun Long ,&nbsp;Jie Wang ,&nbsp;Yian Wang","doi":"10.1016/j.critrevonc.2025.104804","DOIUrl":"10.1016/j.critrevonc.2025.104804","url":null,"abstract":"<div><div>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor secreted by immune and non-immune cells. By binding to specific receptors on target cell surfaces, GM-CSF promotes hematopoiesis, activates immune cells, modulates inflammatory responses, participates in tissue repair, and regulating anti-tumor immunity. Breast cancer is the most prevalent malignancy among women worldwide and the leading cause of cancer-related mortality in females. The pathogenesis of breast cancer is complex, with the tumor microenvironment (TME) playing a pivotal role in disease initiation and progression. The TME comprises malignant tumor cells, immune cells, and stromal cells, where oncogenic mutations in malignant cells drive carcinogenesis and reprogram the functionality of surrounding non-malignant cells through intercellular communication molecules, such as cytokines, chemokines, and extracellular vesicles, thereby promoting or suppressing tumor progression. Beyond its direct effects on tumor cells, GM-CSF exhibits dual roles in the TME: On one hand, it exerts anti-tumor immune effects by activating immune cells, enhancing antigen presentation capacity, and improving tumor vaccine efficacy; on the other hand, it may promote the activation of tumor-associated macrophages, tumor-associated neutrophils, and myeloid-derived suppressor cells, thereby suppressing immune responses and facilitating tumor growth and metastasis. This review systematically summarizes the regulatory roles of GM-CSF in breast cancer progression based on its structure and biological functions, and explores its therapeutic potential through various strategies including vaccine development, combination therapies, and nanoparticle-based delivery systems. These insights may provide novel perspectives for future mechanistic investigations and clinical applications of GM-CSF.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104804"},"PeriodicalIF":5.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295518","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":"IGF-1R inhibitors in cancer: A review of available evidence and future outlook","authors":"Deniz Can Guven ,&nbsp;Jibran Ahmed ,&nbsp;Bettzy Stephen ,&nbsp;Aung Naing","doi":"10.1016/j.critrevonc.2025.104809","DOIUrl":"10.1016/j.critrevonc.2025.104809","url":null,"abstract":"<div><div>The insulin-like growth factor-1 receptor (IGF-1R) has emerged as a critical target in oncology due to its pivotal role in tumor growth, progression, and therapeutic resistance. Despite encouraging preclinical findings, clinical trials utilizing IGF-1R inhibitors as monotherapies have largely been unsuccessful. Herein, we reviewed the available data with IGF-1R inhibitors and the potential of IGF-1R inhibitors when used in combination therapies, an approach supported by advances in precision medicine and immuno-oncology. We aimed to provide comprehensive analysis of the preclinical rationale underpinning the combination of IGF-1R inhibitors with immune checkpoint inhibitors, mTOR/AKT, CDK 4/6, BRAF/MEK, and DNA-damage repair pathway inhibitors. Furthermore, we discussed the development of biomarkers, such as IGF-1R expression levels and hyperglycemia, to predict therapeutic response. Despite initial challenges, the strategic integration of IGF-1R inhibitors within combination therapies holds promise for significantly improving patient outcomes by overcoming resistance. This review highlights the need for ongoing research to optimize these combination strategies and fully harness the therapeutic potential of IGF-1R inhibitors in cancer treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104809"},"PeriodicalIF":5.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318953","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":"Unveilling the potential of liquid biopsy in pancreatic cancer for molecular diagnosis and treatment guidance","authors":"Marta Toledano-Fonseca ,&nbsp;Elena Brozos-Vázquez ,&nbsp;María Victoria García-Ortiz ,&nbsp;Nicolás Costa-Fraga ,&nbsp;Ángel Díaz-Lagares ,&nbsp;Antonio Rodríguez-Ariza ,&nbsp;Rafael López-López ,&nbsp;Enrique Aranda","doi":"10.1016/j.critrevonc.2025.104807","DOIUrl":"10.1016/j.critrevonc.2025.104807","url":null,"abstract":"<div><div>Pancreatic cancer is usually diagnosed at advance stages leading to a poor prognosis and high mortality rates. Furthermore, only a small fraction of patients are elegible for surgery, which is the only curative treatment available. Obtaining tissue biopsies in pancreatic cancer is challenging, often resulting in limited material for molecular tumour analysis. In addition, this procedure involves a considerable risk for patients. The emergence of liquid biopsy in pancreatic cancer has provided a minimally invasive tool for biomarker analysis, improving the diagnosis, prognosis and follow-up of the disease. Consequently, there has been a growing interest in the study of different liquid biopsy-based components, with a special focus on circulating tumor cells (CTCs) and cell-free DNA (cfDNA), but also exploring additional biomarkers such as circulating microRNAs (miRNAs), extracellular vesicles (EVs) or tumor-educated platelets (TEPs). Therefore, this review aims to offer an updated perspective on how these diverse liquid biopsy components can improve the diagnosis, prognosis and monitoring of pancreatic cancer. Additionally, it delves into clinical trials demonstrating that liquid biopsy in pancreatic cancer is becoming an increasingly tangible reality that is ready to integrate into clinical practice.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"212 ","pages":"Article 104807"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303931","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":"Comparison of third-generation tyrosine kinase inhibitor (TKI) ponatinib with first- and second-generation TKIs for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and bias-corrected meta-analysis","authors":"Muhammad Zain Raza,&nbsp;Huzaifa Fayyaz Khwaja,&nbsp;Hafiz Muhammad Ehsan Arshad,&nbsp;Zulnorain,&nbsp;Musab Maqsood,&nbsp;Ali Ahmad Nadeem,&nbsp;Muhammad Omais","doi":"10.1016/j.critrevonc.2025.104806","DOIUrl":"10.1016/j.critrevonc.2025.104806","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), has shown efficacy in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), including cases with and without BCR-ABL1 kinase domain mutations. This meta-analysis compares ponatinib with other TKIs (imatinib, dasatinib, nilotinib etc.) in terms of complete molecular response (CMR), overall survival (OS), and event-free survival (EFS).</div></div><div><h3>Methods</h3><div>A systematic search was conducted across three databases and two clinical trial registries. Pooled odds ratios (ORs) for CMR were calculated using the Mantel-Haenszel method, while hazard ratios (HRs) for OS and EFS were estimated via the inverse variance method. A Bayesian hierarchical model was applied to adjust for biases, providing logOR and logHR estimates.</div></div><div><h3>Results</h3><div>Twelve studies were included. In the uncorrected analysis, ponatinib showed a significant advantage for CMR (OR=2.99; 95 %-CI:2.14–4.18), but this effect was non-significant after bias correction (logOR=0.62; 95 %-CI: −1.17 to 1.35). For OS and EFS, ponatinib demonstrated superior outcomes in both uncorrected [OS: HR= 0.63 (95 %-CI: 0.47–0.83); EFS: HR= 0.62 (95 %-CI: 0.47–0.83)] and bias-corrected analyses [OS: logHR= -1.62 (95 %-CI: −4.02, −0.41); EFS: logHR= -2.94 (95 %-CI: −5.23, −0.58)]. Bias correction indicated an 80.2 % lower risk in OS and a 94.2 % lower risk in EFS with ponatinib. Treatment-related adverse events, reported in six studies, showed no significant differences between ponatinib and other TKIs.</div></div><div><h3>Conclusion</h3><div>Ponatinib is associated with significantly better survival outcomes compared to other TKIs. However, due to limited safety data, future randomized controlled trials are needed to comprehensively evaluate its safety profile relative to other TKIs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104806"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303930","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}