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Scaling data toward pan-cancer foundation models 扩大数据规模,建立泛癌症基础模型
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-11 DOI: 10.1016/j.trecan.2024.08.008
Nadieh Khalili, Francesco Ciompi

Recent advances in artificial intelligence (AI) have revolutionized computational pathology (CPath), particularly through deep learning (DL) and neural networks (NNs). In a recent study, Vorontsov et al. introduced Virchow, a new foundation model (FM) for CPath, which has shown promising results in cancer detection and biomarker prediction.

人工智能(AI)的最新进展给计算病理学(CPath)带来了革命性的变化,特别是通过深度学习(DL)和神经网络(NN)。在最近的一项研究中,Vorontsov 等人为 CPath 引入了一种新的基础模型 (FM)--Virchow,该模型在癌症检测和生物标记预测方面取得了令人鼓舞的成果。
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引用次数: 0
Environmental pollutants and bad bugs work hand in glove 环境污染物和坏虫子狼狈为奸
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-10 DOI: 10.1016/j.trecan.2024.08.007
Dingjiacheng Jia, Shujie Chen

‘Bad bacteria’ could alter the toxicokinetics of environmental pollutants, thereby exacerbating chemically induced tumorigenesis. Recently, Roje et al. reported that specific gut microbiota can metabolize nitrosamine compounds to a toxic oxidation product, aggravating bladder cancer development and progression. These findings have important implications for tumor intervention through the gut microbiota.

坏细菌 "会改变环境污染物的毒物动力学,从而加剧化学诱导的肿瘤发生。最近,Roje 等人报告说,特定的肠道微生物群能将亚硝胺化合物代谢为有毒的氧化产物,从而加剧膀胱癌的发展和恶化。这些发现对通过肠道微生物群干预肿瘤具有重要意义。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-10 DOI: 10.1016/s2405-8033(24)00176-6
No Abstract
无摘要
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引用次数: 0
Subscription & copyright page 订阅和版权页面
IF 18.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-10 DOI: 10.1016/s2405-8033(24)00179-1
No Abstract
无摘要
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引用次数: 0
Transcriptomic subtyping of gastrointestinal malignancies. 胃肠道恶性肿瘤的转录组亚型。
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1016/j.trecan.2024.06.007
Tim R de Back, Sander R van Hooff, Dirkje W Sommeijer, Louis Vermeulen

Gastrointestinal (GI) cancers are highly heterogeneous at multiple levels. Tumor heterogeneity can be captured by molecular profiling, such as genetic, epigenetic, proteomic, and transcriptomic classification. Transcriptomic subtyping has the advantage of combining genetic and epigenetic information, cancer cell-intrinsic properties, and the tumor microenvironment (TME). Unsupervised transcriptomic subtyping systems of different GI malignancies have gained interest because they reveal shared biological features across cancers and bear prognostic and predictive value. Importantly, transcriptomic subtypes accurately reflect complex phenotypic states varying not only per tumor region, but also throughout disease progression, with consequences for clinical management. Here, we discuss methodologies of transcriptomic subtyping, proposed taxonomies for GI malignancies, and the challenges posed to clinical implementation, highlighting opportunities for future transcriptomic profiling efforts to optimize clinical impact.

胃肠道(GI)癌症在多个层面上具有高度异质性。肿瘤异质性可通过分子谱分析来捕捉,如基因、表观遗传、蛋白质组和转录组分类。转录组亚型的优势在于能将遗传和表观遗传信息、癌细胞内在特性和肿瘤微环境(TME)结合起来。不同消化道恶性肿瘤的无监督转录组亚型系统已经引起了人们的兴趣,因为它们揭示了不同癌症的共同生物学特征,并具有预后和预测价值。重要的是,转录组亚型不仅能准确反映每个肿瘤区域的复杂表型状态,还能反映整个疾病进展过程中的表型状态,从而对临床管理产生影响。在此,我们将讨论转录组亚型的方法、消化道恶性肿瘤的分类建议以及临床实施所面临的挑战,并强调未来转录组分析工作的机遇,以优化临床影响。
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引用次数: 0
Precision oncology: current and future platforms for treatment selection. 精准肿瘤学:当前和未来的治疗选择平台。
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI: 10.1016/j.trecan.2024.06.009
Xinran Tang, Michael F Berger, David B Solit

Genomic profiling of hundreds of cancer-associated genes is now a component of routine cancer care. DNA sequencing can identify mutations, mutational signatures, and structural alterations predictive of therapy response and assess for heritable cancer risk, but it has been less useful for identifying predictive biomarkers of sensitivity to cytotoxic chemotherapies, antibody drug conjugates, and immunotherapies. The clinical adoption of molecular profiling platforms such as RNA sequencing better suited to identifying those patients most likely to respond to immunotherapies and drug combinations will be critical to expanding the benefits of precision oncology. This review discusses the potential advantages of innovative molecular and functional profiling platforms designed to replace or complement targeted DNA sequencing and the major hurdles to their clinical adoption.

对数百个癌症相关基因进行基因组分析现已成为常规癌症治疗的一部分。DNA 测序可以确定突变、突变特征和结构改变,预测治疗反应并评估遗传性癌症风险,但在确定对细胞毒性化疗、抗体药物共轭物和免疫疗法敏感性的预测性生物标志物方面作用不大。在临床上采用 RNA 测序等分子剖析平台更适合确定那些最有可能对免疫疗法和药物组合产生反应的患者,这对扩大精准肿瘤学的益处至关重要。本综述讨论了旨在取代或补充 DNA 靶向测序的创新型分子和功能分析平台的潜在优势,以及临床应用的主要障碍。
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引用次数: 0
PARPi, BRCA, and gaps: controversies and future research. PARPi、BRCA 和差距:争议与未来研究。
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.trecan.2024.06.008
Diego Dibitetto, Carmen A Widmer, Sven Rottenberg

In recent years, various poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been approved for the treatment of several cancers to target the vulnerability of homologous recombination (HR) deficiency (e.g., due to BRCA1/2 dysfunction). In this review we analyze the ongoing debates and recent breakthroughs in the use of PARPis for BRCA1/2-deficient cancers, juxtaposing the 'double-strand break (DSB)' and 'single-stranded DNA (ssDNA) gap' models of synthetic lethality induced by PARPis. We spotlight the complexity of this interaction, highlighting emerging research on the role of DNA polymerase theta (POLθ) and ssDNA gaps in shaping therapy responses. We scrutinize the clinical ramifications of these findings, especially concerning PARPi efficacy and resistance mechanisms, underscoring the heterogeneity of BRCA-mutated tumors and the urgent need for advanced research to bridge the gap between laboratory models and patient outcomes.

近年来,各种多聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPis)已被批准用于治疗多种癌症,以针对同源重组(HR)缺陷(如 BRCA1/2 功能障碍所致)的脆弱性。在这篇综述中,我们将 PARPis 诱导合成致死的 "双链断裂 (DSB) "和 "单链 DNA (ssDNA) 间隙 "模型并列起来,分析了在使用 PARPis 治疗 BRCA1/2 缺失型癌症方面正在进行的争论和最近取得的突破。我们强调了这种相互作用的复杂性,重点介绍了有关 DNA 聚合酶 theta (POLθ) 和 ssDNA 缺口在形成治疗反应中的作用的新兴研究。我们仔细研究了这些发现的临床影响,特别是有关 PARPi 的疗效和耐药机制,强调了 BRCA 突变肿瘤的异质性,以及迫切需要先进的研究来弥合实验室模型和患者结果之间的差距。
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引用次数: 0
Mind the gap: why we need to consider teenage and young adult cancers across the research pipeline. 注意差距:为什么我们需要在整个研究过程中考虑青少年癌症?
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-20 DOI: 10.1016/j.trecan.2024.06.010
Laura Danielson, Phil Prime, Rosanna Larter

Historically, teenage and young adult (TYA) cancers have been understudied, with research largely focussing on paediatric or older adult (OA) indications. With increasing TYA cancer incidence rates internationally, now is the time to focus on teenagers and young adults across the research pipeline to improve not only outcomes but also the quality of life for this underserved group.

从历史上看,青少年和年轻人(TYA)癌症一直未得到充分研究,研究主要集中在儿科或老年人(OA)适应症方面。随着青少年和青年癌症发病率在国际上的不断上升,现在正是将青少年和青年癌症作为研究重点的时候,这样不仅能提高治疗效果,还能改善这一未得到充分服务的群体的生活质量。
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引用次数: 0
Metastatic hormone-naïve prostate cancer: a distinct biological entity. 转移性激素无效前列腺癌:一种独特的生物学实体。
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-23 DOI: 10.1016/j.trecan.2024.06.005
Jon Corres-Mendizabal, Francesca Zacchi, Natalia Martín-Martín, Joaquin Mateo, Arkaitz Carracedo

Metastatic hormone-naïve prostate cancer (mHNPC) is often the initial form of presentation for metastatic prostate cancer and encompasses a heterogeneous patient population with high inter-patient heterogeneity in prognosis and response to therapy. A more precise treatment of mHNPC, guided by evidence-based biomarkers, remains an unmet medical need. In addition, the limited number of representative laboratory models of mHNPC hampers the translation of basic research into clinical applications. We provide a comprehensive overview of the clinical and biological features that characterize mHNPC, highlight molecular data that could explain the unique prognostic characteristics of mHNPC, and identify key open questions.

转移性激素无效前列腺癌(mHNPC)通常是转移性前列腺癌的最初表现形式,它包括一个在预后和治疗反应方面具有高度异质性的异质性患者群体。以循证生物标志物为指导,对 mHNPC 进行更精确的治疗,仍是一项尚未满足的医疗需求。此外,具有代表性的 mHNPC 实验室模型数量有限,阻碍了基础研究向临床应用的转化。我们全面概述了 mHNPC 的临床和生物学特征,重点介绍了可以解释 mHNPC 独特预后特征的分子数据,并确定了关键的开放性问题。
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引用次数: 0
Small molecules targeting microRNAs: new opportunities and challenges in precision cancer therapy. 靶向 microRNA 的小分子:癌症精准治疗的新机遇与挑战。
IF 14.3 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1016/j.trecan.2024.06.006
Ancuta Jurj, Beatrice Fontana, Gabriele Varani, George A Calin

Noncoding RNAs, especially miRNAs, play a pivotal role in cancer initiation and metastasis, underscoring their susceptibility to precise modulation via small molecule inhibitors. This review examines the innovative strategy of targeting oncogenic miRNAs with small drug-like molecules, an approach that can reshape the cancer treatment landscape. We review the current understanding of the multifaceted roles of miRNAs in oncogenesis, highlighting emerging therapeutic paradigms that have the potential to expand cancer treatment options. As research on small molecule inhibitors of miRNA is still in its early stages, ongoing investigative efforts and the development of new technologies and chemical matter are essential to fulfill the significant potential of this innovative approach to cancer treatment.

非编码 RNA,尤其是 miRNA,在癌症的诱发和转移过程中发挥着关键作用,这说明它们很容易受到小分子抑制剂的精确调控。本综述探讨了用类药物小分子靶向致癌 miRNA 的创新策略,这种方法可以重塑癌症治疗格局。我们回顾了目前对 miRNA 在致癌过程中多方面作用的理解,重点介绍了有可能扩大癌症治疗选择的新兴治疗范例。由于对 miRNA 小分子抑制剂的研究仍处于早期阶段,持续的研究工作以及新技术和化学物质的开发对于发挥这种创新癌症治疗方法的巨大潜力至关重要。
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Trends in cancer
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