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Targeted Therapy with Polymeric Nanoparticles in PBRM1-Mutant Biliary Tract Cancers: Harnessing DNA Damage Repair Mechanisms. 聚合纳米粒子对 PBRM1 突变胆道癌的靶向治疗:利用 DNA 损伤修复机制。
IF 6.2 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-08 DOI: 10.1016/j.critrevonc.2024.104505
Hrushikesh Wagh,Sankha Bhattacharya
Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10% of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.
胆道癌(BTC)是一种侵袭性恶性肿瘤,预后不佳,需要强化靶向治疗。约 10% 的胆道癌存在 PBRM1 基因突变,这种突变会阻碍 DNA 损伤修复途径,使癌细胞更容易受到 DNA 损伤化学物质的伤害。本综述重点介绍基于聚乳酸-聚乙二醇酸(PLGA)的纳米颗粒靶向递送系统的开发情况,该系统可选择性地将化疗药物递送至PBRM1缺陷的BTC细胞。这些纳米颗粒可提高药物在肿瘤部位的靶向性和滞留性,从而改善疗效。在临床前研究中,这种纳米粒子的药代动力学特征令人鼓舞,并支持其在肿瘤内实现高药物蓄积和延长循环时间的能力。综述还强调了 Pou3F3:I54N 在加快生物测定以选择 BTC 靶向治疗患者方面的潜力。
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引用次数: 0
PROTON THERAPY FOR ADULT-TYPE DIFFUSE GLIOMA: A SYSTEMATIC REVIEW. 质子治疗成人型弥漫性胶质瘤:系统综述。
IF 6.2 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.critrevonc.2024.104501
Nicolas Goliot,Selim Mohssine,Dinu Stefan,Arthur Leclerc,Evelyne Emery,Jeanne Riverain,Fernand Missohou,Julien Geffrelot,William Kao,Samuel Valable,Jacques Balosso,Paul Lesueur
BACKGROUNDWe conducted a systematic review to evaluate outcomes and toxicities associated with proton therapy in the treatment of adult-type diffuse glioma.METHODSFollowing PRISMA guidelines, we searched PubMed for both prospective and retrospective studies on proton therapy for adult diffuse gliomas, including low-grade gliomas and glioblastomas. Survival and toxicity outcomes were reported separately for these glioma types.RESULTSTwelve studies from 2013 to 2023 were selected, comprising 3 prospective and 9 retrospective studies. The analysis covered 570 patients with low-grade gliomas and 240 patients with glioblastoma or WHO grade 4 gliomas. Proton therapy was found to be comparable to conventional radiotherapy in terms of survival outcomes. Its main advantage is the ability to minimize radiation exposure to healthy tissues.DISCUSSIONProton therapy offers comparable survival outcomes to conventional radiotherapy for adult diffuse gliomas and may enhance treatment tolerance, especially regarding neurocognitive function. A major limitation of this review is the predominance of retrospective studies. Future research should ensure rigorous patient selection and adhere to the latest WHO 2021 classification.
背景我们进行了一项系统性综述,以评估质子疗法治疗成人型弥漫性胶质瘤的相关结果和毒性。方法根据PRISMA指南,我们在PubMed上检索了有关质子疗法治疗成人弥漫性胶质瘤(包括低级别胶质瘤和胶质母细胞瘤)的前瞻性和回顾性研究。结果选取了2013年至2023年的12项研究,包括3项前瞻性研究和9项回顾性研究。分析涵盖了570名低度胶质瘤患者和240名胶质母细胞瘤或WHO 4级胶质瘤患者。研究发现,质子疗法在生存率方面与传统放疗不相上下。讨论 质子疗法为成人弥漫性胶质瘤提供了与传统放疗相当的生存率,并可提高治疗耐受性,尤其是在神经认知功能方面。本综述的一个主要局限是以回顾性研究为主。未来的研究应确保严格选择患者,并遵循最新的WHO 2021分类。
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引用次数: 0
The Potential of Circulating Cell-Free RNA in CNS Tumor Diagnosis and Monitoring: A Liquid Biopsy Approach. 循环游离细胞 RNA 在中枢神经系统肿瘤诊断和监测中的潜力:液体活检方法
IF 6.2 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.critrevonc.2024.104504
Carlos Pilotto Heming,Veronica Aran
Early detection of malignancies, through regular cancer screening, has already proven to have potential to increase survival rates. Yet current screening methods rely on invasive, expensive tissue sampling that has hampered widespread use. Liquid biopsy is noninvasive and represents a potential approach to precision oncology, based on molecular profiling of body fluids. Among these, circulating cell-free RNA (cfRNA) has gained attention due to its diverse composition and potential as a sensitive biomarker. This review provides an overview of the processes of cfRNA delivery into the bloodstream and the role of cfRNA detection in the diagnosis of central nervous system (CNS) tumors. Different types of cfRNAs such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been recognized as potential biomarkers in CNS tumors. These molecules exhibit differential expression patterns in the plasma, cerebrospinalfluid (CSF) and urine of patients with CNS tumors, providing information for diagnosing the disease, predicting outcomes, and assessing treatment effectiveness. Few clinical trials are currently exploring the use of liquid biopsy for detecting and monitoring CNS tumors. Despite obstacles like sample standardization and data analysis, cfRNA shows promise as a tool in the diagnosis and management of CNS tumors, offering opportunities for early detection, personalized therapy, and improved patient outcomes.
事实证明,通过定期癌症筛查及早发现恶性肿瘤有可能提高存活率。然而,目前的筛查方法依赖于侵入性、昂贵的组织取样,这阻碍了筛查方法的广泛应用。液体活检是一种非侵入性的方法,是基于体液分子谱分析的精准肿瘤学的一种潜在方法。其中,循环无细胞 RNA(cfRNA)因其多样的组成和作为灵敏生物标记物的潜力而备受关注。本综述概述了 cfRNA 进入血液的过程以及 cfRNA 检测在中枢神经系统(CNS)肿瘤诊断中的作用。不同类型的 cfRNA,如 microRNA(miRNA)、长非编码 RNA(lncRNA)和环状 RNA(circRNA)已被认为是中枢神经系统肿瘤的潜在生物标记物。这些分子在中枢神经系统肿瘤患者的血浆、脑脊液(CSF)和尿液中表现出不同的表达模式,为诊断疾病、预测预后和评估治疗效果提供了信息。目前,很少有临床试验在探索使用液体活检检测和监测中枢神经系统肿瘤。尽管存在样本标准化和数据分析等障碍,cfRNA 仍有望成为中枢神经系统肿瘤诊断和管理的工具,为早期检测、个性化治疗和改善患者预后提供机会。
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引用次数: 0
Definitive radiotherapy and trismus in HNC patients: A critical review HNC患者的确定性放疗与三联症:评论性综述。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-27 DOI: 10.1016/j.critrevonc.2024.104486

Introduction

Trismus is a potentially critical morbidity following curative-intended radiotherapy in head and neck cancer patients. However, in this setting, evidence regarding this side effect remains to be fully defined, particularly in terms of dosimetric parameters.

Materials and Methods

Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used.

Results

This paper contains a narrative report and a critical discussion of the evidence on radiation-induced trismus in the literature, particularly the dosimetric concerns.

Conclusions

The treatment goal should be to maintain high cure rates and limit the onset of complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring.

简介头颈部癌症患者在接受治疗性放疗后,可能会出现严重的三凹症状。然而,在这种情况下,有关这种副作用的证据仍有待全面界定,特别是在剂量参数方面:主要参考文献来自 PubMed 查询。结果:本文对文献中有关辐射诱发三体症的证据进行了叙述性报告和批判性讨论,尤其是剂量学方面的问题:结论:治疗目标应是保持高治愈率并限制并发症的发生。有必要进一步评估剂量测量和临床结果,以确定高风险患者,从而有针对性地进行治疗。
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引用次数: 0
Role of mitochondria and potential of mitochondria-targeted therapy in BRAF mutant cancer: A review 线粒体在 BRAF 突变癌症中的作用和线粒体靶向疗法的潜力:综述。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-26 DOI: 10.1016/j.critrevonc.2024.104484

The classical mitogen-activated protein kinase (MAPK) signaling pathway, the Ras/Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK protein kinase cascade, is a conserved cascade that regulates cell growth, differentiation, and proliferation. The significance of BRAF in cancer was established with the discovery of cancer-activating mutations in BRAF in several human tumors in 2002. Currently, BRAF is recognized as a driver mutation that affects cancer phenotypes in different ways, making it an important therapeutic target for cancer. BRAF-selective inhibitors have shown promise in clinical trials involving patients with metastatic melanoma. However, resistance mechanisms to BRAF inhibitors therapy have resulted in short-lived therapeutic responses. Further in-depth research is imperative to explore resistance mechanisms that oppose the effectiveness of BRAF inhibitors. Metabolic reprogramming has emerging role in BRAF-mutant cancers. In particular, mitochondrial metabolism and its closely related signaling pathways mediated by mitochondria have become recognized as potential new targets for treating BRAF-mutant cancers. This review, examines the progress in understanding BRAF mutations in cancer, the clinicopathological correlation of BRAF inhibitors, and recent advances in mitochondrial metabolism, mitochondrial dynamics and mitochondrial mediated death in BRAF-mutant cancer. This review will inform future cancer research and lay the foundation for novel treatment combinations of BRAF-mutant cancers.

经典的有丝分裂原激活蛋白激酶(MAPK)信号通路,即 Ras/Raf/MEK(有丝分裂原激活蛋白激酶/ERK 激酶)/ERK 蛋白激酶级联,是一种调节细胞生长、分化和增殖的保守级联。2002 年,在几种人类肿瘤中发现了 BRAF 的癌症激活突变,从而确定了 BRAF 在癌症中的重要性。目前,BRAF 被认为是一种以不同方式影响癌症表型的驱动突变,使其成为癌症的重要治疗靶点。在涉及转移性黑色素瘤患者的临床试验中,BRAF 选择性抑制剂已显示出治疗前景。然而,BRAF抑制剂疗法的耐药机制导致了短暂的治疗反应。当务之急是开展进一步的深入研究,以探索阻碍 BRAF 抑制剂疗效的耐药机制。代谢重编程在 BRAF 突变癌症中扮演着新的角色。尤其是线粒体代谢及其密切相关的由线粒体介导的信号通路已被认为是治疗 BRAF 突变癌症的潜在新靶点。本综述探讨了对癌症中 BRAF 突变的认识进展、BRAF 抑制剂的临床病理学相关性,以及 BRAF 突变癌症中线粒体代谢、线粒体动力学和线粒体介导的死亡的最新进展。本综述将为未来的癌症研究提供参考,并为 BRAF 突变癌症的新型治疗组合奠定基础。
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引用次数: 0
Metabolic interactions of host-gut microbiota: New possibilities for the precise diagnosis and therapeutic discovery of gastrointestinal cancer in the future—A review 宿主-肠道微生物群的代谢相互作用:未来胃肠癌精确诊断和治疗发现的新可能性--综述。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.critrevonc.2024.104480

Gastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.

胃肠道(GI)癌症继续对全球健康构成重大挑战。最近,我们对宿主和肠道微生物群之间复杂关系的认识取得了进展,揭示了代谢相互作用在消化道癌症的发病和进展过程中的关键作用。在这项研究中,我们探讨了微生物群如何与宿主相互作用,影响影响消化道肿瘤形成的信号通路。此外,我们还研究了操纵消化道微生物群用于临床的潜在治疗方法。揭示宿主与肠道微生物群之间复杂的分子交换有助于更深入地了解驱动癌症发展的潜在机制。代谢相互作用有望确定与癌症特定阶段相关的微生物特征或代谢途径。因此,这项研究为消化道癌症的诊断、治疗和管理提供了潜在的策略,以改善患者的预后。
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引用次数: 0
Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors 揭示循环肿瘤细胞的影响:二十年来实体瘤的发现与临床进展。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-17 DOI: 10.1016/j.critrevonc.2024.104483

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care.

循环肿瘤细胞(CTCs)计数和分子图谱分析有望彻底改变实体瘤的治疗。在过去二十年里,人们对循环肿瘤细胞的认识有了长足的发展,其中包括各种恶性肿瘤的重要生物学发现和临床研究。对于某些肿瘤类型,如乳腺癌、前列腺癌和结直肠癌,CTCs 已经可以进入临床实践,但对于其他肿瘤类型,还需要进行更多的研究。CTCs 可作为多功能生物标记物,为肿瘤生物学、转移进展和治疗反应提供洞察力。本综述总结了 CTC 研究的最新进展,并强调了未来的研究方向。其中特别关注对 CTC 和其他循环生物标记物(尤其是循环肿瘤 DNA)的同时评估。多重分析评估有可能释放液体活检的全部临床功能。总之,CTCs 是精准肿瘤学中一种变革性的生物标记物,为将科学发现转化为切实改善患者护理提供了难得的机会。
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引用次数: 0
Unleashing precision: A review of targeted approaches in pleural mesothelioma 释放精准:胸膜间皮瘤靶向治疗方法综述。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-17 DOI: 10.1016/j.critrevonc.2024.104481

This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers. Targeting genotypic and phenotypic alterations emerges as a promising avenue, demanding precision oncology in this rare disease. CDKN2A loss, prevalent in PM, may respond to CDK4/6 inhibitors. Defects in MMR and HR suggest tailored approaches with ICI or PARP inhibitors, respectively. Ongoing trials explore novel inhibitors and promising targets like mesothelin. Implementing these strategies requires overcoming challenges in patient selection, combination therapies, biomarker identification, and cost considerations. Collaboration is crucial for transforming these insights into impactful clinical interventions, heralding the era of personalized and precision medicine for PM.

这篇综述深入探讨了胸膜间皮瘤(PM)错综复杂的病因,强调了细微治疗策略的必要性。虽然以铂为基础的化疗仍是基石,但免疫检查点抑制剂(ICIs)的出现,特别是通过Checkmate 743试验,重塑了治疗范式。由于患者的异质性和缺乏特异性生物标志物,挑战依然存在。以基因型和表型改变为靶点是一条大有可为的途径,对这种罕见疾病的精准肿瘤学提出了更高的要求。CDKN2A缺失在肺癌中很常见,可能会对CDK4/6抑制剂产生反应。MMR和HR的缺陷分别提示了使用ICI或PARP抑制剂的定制方法。目前正在进行的试验正在探索新型抑制剂和MSLN等有希望的靶点。实施这些策略需要克服患者选择、联合疗法、生物标记物鉴定和成本考虑等方面的挑战。要将这些见解转化为有影响力的临床干预措施,预示着针对 PM 的个性化和精准医疗时代的到来,合作至关重要。
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引用次数: 0
A neuroendocrine biomarker revolution from monoanalyte to multianalyte biomarkers in non-functioning gastro-entero-pancreatic neuroendocrine neoplasms 非功能性胃肠胰神经内分泌肿瘤的神经内分泌生物标志物革命--从单一分析物到多分析物生物标志物。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-15 DOI: 10.1016/j.critrevonc.2024.104460

Neuroendocrine neoplasms (NENs) arise from neuroendocrine cells in a wide variety of organs. One of the most affected disease sites is the gastrointestinal system, which originates the gastro-entero-pancreatic NENs (GEP-NENs), a heterogenous group of malignancies that are rapidly increasing in incidence. These tumors can be functioning, with secretory activity leading to identifiable clinical syndromes, or non-functioning, with no secretory activity but with local symptoms of tumor growth and metastasis. A limitation in biomarkers is a crucial unmet need in non-secretory NEN management, as clinical decision-making is made more difficult by obstacles in tumor classification, prognostic evaluation, assessment of treatment response and surveillance. The objective of this review is to present existing and novel biomarkers for NENs that can function as prognostic factors and monitor disease progression or regression longitudinally, with a special emphasis on innovative research into novel multianalyte biomarkers.

神经内分泌肿瘤(NENs)产生于多种器官的神经内分泌细胞。受影响最大的疾病部位之一是胃肠系统,胃肠胰腺神经内分泌肿瘤(GEP-NENs)就起源于此,这是一组发病率迅速上升的异质性恶性肿瘤。这些肿瘤可以是功能性的,具有分泌活性,导致可识别的临床综合征;也可以是非功能性的,没有分泌活性,但有肿瘤生长和转移的局部症状。由于肿瘤分类、预后评估、治疗反应评估和监测方面的障碍使临床决策变得更加困难,因此生物标志物的局限性是非分泌性 NEN 管理中尚未满足的关键需求。本综述旨在介绍可作为预后因素和纵向监测疾病进展或消退的现有和新型 NEN 生物标志物,并特别强调对新型多分析生物标志物的创新研究。
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引用次数: 0
Clinical applications of radiomics and deep learning in breast and lung cancer: A narrative literature review on current evidence and future perspectives 放射组学和深度学习在乳腺癌和肺癌中的临床应用:关于当前证据和未来前景的叙述性文献综述。
IF 5.5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.critrevonc.2024.104479

Radiomics, analysing quantitative features from medical imaging, has rapidly become an emerging field in translational oncology. Radiomics has been investigated in several neoplastic malignancies as it might allow for a non-invasive tumour characterization and for the identification of predictive and prognostic biomarkers. Over the last few years, evidence has been accumulating regarding potential clinical applications of machine learning in many crucial moments of cancer patients’ history. However, the incorporation of radiomics in clinical decision-making process is still limited by low data reproducibility and study variability. Moreover, the need for prospective validations and standardizations is emerging. In this narrative review, we summarize current evidence regarding radiomic applications in high-incidence cancers (breast and lung) for screening, diagnosis, staging, treatment choice, response, and clinical outcome evaluation. We also discuss pro and cons of the radiomic approach, suggesting possible solutions to critical issues which might invalidate radiomics studies and propose future perspectives.

放射组学分析医学成像的定量特征,已迅速成为转化肿瘤学的一个新兴领域。放射组学已在几种恶性肿瘤中进行了研究,因为它可以进行非侵入性肿瘤特征描述,并确定预测性和预后性生物标志物。在过去几年中,有关机器学习在癌症患者病史中许多关键时刻的潜在临床应用的证据不断积累。然而,将放射组学纳入临床决策过程仍受到数据可重复性低和研究变异性的限制。此外,前瞻性验证和标准化的需求也在不断涌现。在这篇叙述性综述中,我们总结了目前有关放射组学应用于高发癌症(乳腺癌和肺癌)筛查、诊断、分期、治疗选择、反应和临床结果评估的证据。我们还讨论了放射线组学方法的利弊,对可能导致放射线组学研究无效的关键问题提出了可能的解决方案,并提出了未来展望。
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引用次数: 0
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Critical reviews in oncology/hematology
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