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Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer 将循环肿瘤 DNA 作为可切除非小细胞肺癌的预后生物标记物
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.trecan.2024.04.004
Chris Abbosh, Darren Hodgson, Gary J. Doherty, Davina Gale, James R.M. Black, Leora Horn, Jorge S. Reis-Filho, Charles Swanton

Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor–node–metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.

可切除非小细胞肺癌(NSCLC)的全身治疗正随着新辅助、围手术期和辅助免疫疗法方法的出现而不断发展。在临床诊断、新辅助治疗期间或切除术后进行循环肿瘤DNA(ctDNA)检测,可发现可能从治疗升级或转换中获益的高危患者。本综述总结了支持基于ctDNA确定NSCLC风险的数据的转化意义,以及有关ctDNA作为预后生物标记物的有效性/效用的未决问题。我们讨论了新出现的ctDNA功能,以完善肺腺癌的临床肿瘤-结节-转移(TNM)分期;新辅助治疗期间ctDNA的动态变化,以确定获得次优疗效的患者;以及术后分子残留病(MRD)检测,以升级全身治疗。考虑到地标性 MRD 阴性/MRD 阳性患者的不同复发特征,我们提出了如何将 ctDNA 与病理反应数据相结合,以优化术后风险分层。
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引用次数: 0
Biosocial determinants inform on enduring cancer disparities 生物社会决定因素为癌症的持久性差异提供信息
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.trecan.2024.05.004
David P. Turner, Robert A. Winn, Victoria J. Findlay

Social, environmental, and biological risk factors influence exposures to newly termed ‘biosocial determinants of health’. As molecular factors that lie at the intersection between lived experiences and individual biology, biosocial determinants may inform on the enduring complexity of cancer disparity across transdisciplinary studies.

社会、环境和生物风险因素影响着新近被称为 "健康的生物社会决定因素 "的暴露。生物社会决定因素是生活经历与个体生物学之间的分子因素,可为跨学科研究中癌症差异的持久复杂性提供信息。
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引用次数: 0
Emerging roles of TBK1 in cancer immunobiology. TBK1 在癌症免疫生物学中的新作用。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-21 DOI: 10.1016/j.trecan.2024.02.007
Alex Miranda, Carl A Shirley, Russell W Jenkins

TANK-binding kinase 1 (TBK1) is a versatile serine/threonine protein kinase with established roles in innate immunity, metabolism, autophagy, cell death, and inflammation. While best known for its role in regulating innate immunity, TBK1 has emerged as a cancer cell-intrinsic immune evasion gene by virtue of its role in modulating cellular responses to inflammatory signals emanating from the immune system. Beyond its effect on cancer cells, TBK1 appears to regulate lymphoid and myeloid cells in the tumor immune microenvironment. In this review, we detail recent advances in our understanding of the tumor-intrinsic and -extrinsic roles and regulation of TBK1 in tumor immunity.

TANK 结合激酶 1(TBK1)是一种多功能丝氨酸/苏氨酸蛋白激酶,在先天性免疫、新陈代谢、自噬、细胞死亡和炎症中发挥着既定的作用。TBK1 因其在调节先天性免疫中的作用而闻名,但由于其在调节细胞对来自免疫系统的炎症信号的反应方面的作用,它已成为一种癌细胞内在免疫逃避基因。除了对癌细胞的影响,TBK1 似乎还能调节肿瘤免疫微环境中的淋巴细胞和骨髓细胞。在这篇综述中,我们将详细介绍最近在了解 TBK1 在肿瘤免疫中的内在和外在作用和调控方面取得的进展。
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引用次数: 0
Intracranial CAR-T cell delivery in glioblastoma patients. 为胶质母细胞瘤患者提供颅内 CAR-T 细胞。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-22 DOI: 10.1016/j.trecan.2024.05.002
Philippa Vaughn-Beaucaire, Moon Jung Choi, Olin Liang, Sean E Lawler

Chimeric antigen receptor (CAR)-T cell therapy is emerging as a promising approach for improving outcomes in high-grade glioma. Here, we highlight three recent studies that reported safety and feasibility of intracranial CAR-T cell administration in patients with glioblastoma (GBM) as well as preliminary evidence of potential responses, supporting further investigations of this approach.

嵌合抗原受体(CAR)-T 细胞疗法正在成为改善高级别胶质瘤治疗效果的一种有前途的方法。在此,我们重点介绍最近的三项研究,这些研究报告了在胶质母细胞瘤(GBM)患者中进行颅内 CAR-T 细胞给药的安全性和可行性,以及潜在反应的初步证据,支持对这种方法的进一步研究。
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引用次数: 0
Chromatin as an old and new anticancer target 染色质作为新老抗癌靶点
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.trecan.2024.05.005
Jacques Neefjes, Katerina Gurova, Jay Sarthy, Gábor Szabó, Steven Henikoff

Recent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated classes of genes across all cancers. However, chemotherapies developed for cancers involving DNA damage remain the standard of care for chromatin-deranged malignancies. In this review we address this conundrum by establishing the concept of ‘chromatin damage’: the non-genetic damage to protein–DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of overlooked chromatin-targeting agents. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.

最近的全基因组分析发现,染色质修饰因子是所有癌症中最常发生突变的一类基因。然而,针对涉及DNA损伤的癌症开发的化疗方法仍然是染色质受损恶性肿瘤的治疗标准。在这篇综述中,我们通过建立 "染色质损伤 "的概念来解决这一难题:某些小分子诱导的蛋白质-DNA相互作用的非遗传性损伤。我们重点介绍了蒽环类药物,这是一类广泛应用于肿瘤学的化疗药物,也是被忽视的染色质靶向药物的一个例子。我们讨论了目前对这一现象的理解,并探讨了新出现的染色质损伤药物,以此作为进一步研究的基础,最大限度地发挥它们在现代癌症治疗中的作用。
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引用次数: 0
The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments. 乳腺癌的抗癌免疫反应:当前和新兴的生物标记物与治疗方法。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-22 DOI: 10.1016/j.trecan.2024.02.008
Victoria C Rayson, Michael A Harris, Peter Savas, Michael L Hun, Balaji Virassamy, Roberto Salgado, Sherene Loi

Triple-negative breast cancers (TNBCs) exhibit heightened T cell infiltration, contributing to an enhanced response to immune checkpoint blockade (ICB) compared with other subtypes. An immune-rich immune microenvironment correlates with improved prognosis in early and advanced TNBC. Combination chemotherapy and ICB is now the standard of care in early- and late-stage TNBC. Although programmed death ligand-1 (PD-L1) positivity predicts ICB response in advanced stages, its role in early-stage disease remains uncertain. Despite neoadjuvant ICB becoming common in early-stage TNBC, the necessity of adjuvant ICB after surgery remains unclear. Understanding the molecular basis of the immune response in breast cancer is vital for precise biomarkers for ICB and effective combination therapy strategies.

与其他亚型相比,三阴性乳腺癌(TNBC)表现出更高的T细胞浸润,从而增强了对免疫检查点阻断(ICB)的反应。免疫丰富的免疫微环境与早期和晚期 TNBC 的预后改善相关。联合化疗和 ICB 是目前治疗早期和晚期 TNBC 的标准方法。虽然程序性死亡配体-1(PD-L1)阳性可预测晚期患者对 ICB 的反应,但其在早期疾病中的作用仍不确定。尽管新辅助 ICB 已成为早期 TNBC 的常见疗法,但术后辅助 ICB 的必要性仍不明确。了解乳腺癌免疫反应的分子基础对于确定 ICB 的精确生物标志物和制定有效的联合治疗策略至关重要。
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引用次数: 0
Nanomedicine to aid immunogenic cell death (ICD)-based anticancer therapy. 纳米药物辅助基于免疫原性细胞死亡(ICD)的抗癌疗法。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-29 DOI: 10.1016/j.trecan.2024.03.003
Robin Demuynck, Yanou Engelen, André G Skirtach, Stefaan C De Smedt, Ine Lentacker, Dmitri V Krysko

Immunogenic cell death (ICD) is emerging as a key component of antitumor therapy that harnesses the immune system of the patient to combat cancer. In recent years, several efforts were made to improve the ICD-based therapies. Here, we discuss how nanomaterial-based strategies increase the efficacy of ICD and highlight their benefits and challenges.

免疫性细胞死亡(ICD)正在成为抗肿瘤疗法的一个关键组成部分,它能利用患者的免疫系统来对抗癌症。近年来,人们为改进基于免疫细胞死亡的疗法做出了许多努力。在此,我们将讨论基于纳米材料的策略如何提高 ICD 的疗效,并强调其优势和挑战。
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引用次数: 0
Puzzling phenomenon: adult-onset cancer predisposition and pediatric cancer. 令人费解的现象:成人致癌倾向与小儿癌症。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-19 DOI: 10.1016/j.trecan.2024.02.011
Michaela Kuhlen, Thomas G Hofmann, Monika M Golas

Pathogenic variants (PVs) in DNA repair-linked adult-onset cancer predisposition genes, including double heterozygosity, are increasingly identified in pediatric patients with cancer. Their role in childhood cancer, however, remains poorly understood. Integrating comprehensive tumor analysis is integral for understanding the contribution of such PVs in cancer development and personalized cancer care.

在儿童癌症患者中,越来越多地发现了与 DNA 修复相关的成人发病癌症易感基因中的致病变异(PVs),包括双杂合子。然而,人们对它们在儿童癌症中的作用仍然知之甚少。综合全面的肿瘤分析是了解此类 PV 在癌症发展和个性化癌症治疗中的作用所不可或缺的。
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引用次数: 0
Lifileucel: the first cellular therapy approved for solid tumours. Lifileucel:首个获准用于实体瘤的细胞疗法。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1016/j.trecan.2024.04.003
Max Julve, Mark P Lythgoe, James Larkin, Andrew J S Furness

The US Food and Drug Administration (FDA) approval of lifileucel, for advanced melanoma, represents the first cellular therapy to reach the clinic for solid cancers. Here, we summarise this landmark approval, consider the associated regulatory pathway, and evaluate the challenges that remain to ensure effective implementation of this advanced 'living' therapy.

美国食品和药物管理局(FDA)批准使用lifileucel治疗晚期黑色素瘤,这是首个用于实体瘤临床治疗的细胞疗法。在此,我们总结了这一具有里程碑意义的批准,考虑了相关的监管途径,并评估了为确保有效实施这种先进的 "活 "疗法所面临的挑战。
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引用次数: 0
Targeting phagocytosis to enhance antitumor immunity: (Trends in Cancer, 9:8 p:650-665, 2023). 靶向吞噬作用以增强抗肿瘤免疫:(《癌症趋势》,9:8 p:650-6652023)。
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2023-10-13 DOI: 10.1016/j.trecan.2023.09.009
Kristin Huntoon, DaeYong Lee, Shiyan Dong, Abin Antony, Betty Y S Kim, Wen Jiang
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Trends in cancer
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