Biochimica et biophysica acta. Reviews on cancer最新文献_第8页

The potential of TRP channels as new prognostic and therapeutic targets against prostate cancer progression TRP 通道作为抗击前列腺癌进展的新预后和治疗靶点的潜力。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189226

Giorgia Chinigò, Federico Alessandro Ruffinatti, Luca Munaron

Prostate cancer (PCa) is the second deadliest cancer among men worldwide. Particularly critical is its development towards metastatic androgen-independent forms for which the current therapies are ineffective. Indeed, the 5-year relative survival for PCa drops dramatically to 34 % in the presence of metastases. The superfamily of Transient Receptor Potential (TRP) channels could answer the urgent request to identify new prognostic and therapeutic tools against metastatic PCa. Indeed, this class of ion channels revealed an appealing de-regulation during PCa development and its progression towards aggressive forms. Altered expression and/or functionality of several TRPs have been associated with the PCa metastatic cascade by significantly impacting tumor growth, invasiveness, and angiogenesis. In this review, we will dissect the contribution of TRP channels in such hallmarks of PCa and then discuss their applicability as new prognostic and therapeutic agents in the fight against metastatic PCa. In particular, the great potential of TRPM8, TRPV6, and TRPA1 in opening the way to new treatment perspectives will be highlighted.

前列腺癌（PCa）是全球第二致命的男性癌症。尤为关键的是，前列腺癌会发展为转移性雄激素依赖型，而目前的治疗方法对其无效。事实上，如果出现转移，PCa 的 5 年相对存活率会急剧下降至 34%。瞬时受体电位（TRP）通道超家族可以满足人们的迫切要求，即找到新的预后和治疗工具来对抗转移性 PCa。事实上，这类离子通道在 PCa 的发展及其向侵袭性形式发展的过程中显示出了诱人的失调。几种 TRPs 的表达和/或功能改变与 PCa 转移级联相关，对肿瘤生长、侵袭性和血管生成有显著影响。在这篇综述中，我们将剖析 TRP 通道在 PCa 这些特征中的作用，然后讨论它们作为新的预后和治疗药物在对抗转移性 PCa 中的适用性。我们将特别强调 TRPM8、TRPV6 和 TRPA1 在开辟新的治疗前景方面的巨大潜力。

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引用次数: 0

Biomarkers in high grade serous ovarian cancer 高级别浆液性卵巢癌的生物标志物

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189224

Mark Bates PhD , Bashir M. Mohamed PhD , Faye Lewis MSc , Sharon O’Toole PhD , John J. O’Leary MD, DSc, PhD

High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. HGSC patients typically present with advanced disease, which is often resistant to chemotherapy and recurs despite initial responses to therapy, resulting in the poor prognosis associated with this disease. There is a need to utilise biomarkers to manage the various aspects of HGSC patient care. In this review we discuss the current state of biomarkers in HGSC, focusing on the various available immunohistochemical (IHC) and blood-based biomarkers, which have been examined for their diagnostic, prognostic and theranostic potential in HGSC. These include various routine clinical IHC biomarkers such as p53, WT1, keratins, PAX8, Ki67 and p16 and clinical blood-borne markers and algorithms such as CA125, HE4, ROMA, RMI, ROCA, and others. We also discuss various components of the liquid biopsy as well as a number of novel IHC biomarkers and non-routine blood-borne biomarkers, which have been examined in various ovarian cancer studies. We also discuss the future of ovarian cancer biomarker research and highlight some of the challenges currently facing the field.

高级别浆液性卵巢癌（HGSC）是卵巢癌中最常见的亚型。高分化浆液性卵巢癌患者通常是晚期患者，对化疗通常有耐药性，尽管最初对治疗有反应，但仍会复发，因此这种疾病的预后较差。有必要利用生物标志物来管理 HGSC 患者护理的各个方面。在这篇综述中，我们将讨论 HGSC 生物标志物的现状，重点是各种可用的免疫组化（IHC）和血液生物标志物，这些生物标志物在 HGSC 的诊断、预后和治疗方面的潜力已得到研究。其中包括各种常规临床 IHC 生物标记物，如 p53、WT1、角蛋白、PAX8、Ki67 和 p16，以及临床血液标记物和算法，如 CA125、HE4、ROMA、RMI、ROCA 等。我们还讨论了液体活检的各种成分以及一些新型 IHC 生物标记物和非常规血源性生物标记物，这些标记物已在各种卵巢癌研究中得到检验。我们还讨论了卵巢癌生物标记物研究的未来，并强调了该领域目前面临的一些挑战。

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引用次数: 0

An updated outlook on autophagy mechanism and how it supports acute myeloid leukemia maintenance 自噬机制及其如何支持急性髓性白血病维持的最新展望。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189214

Brunno Gilberto Santos de Macedo , Manuela Albuquerque de Melo , Diego Antonio Pereira-Martins , João Agostinho Machado-Neto , Fabiola Traina

The gradual acquisition of genetic and epigenetic disturbances bestows malignant traits upon hematopoietic stem cells, subverting them into a founder and reservoir cell for de novo acute myeloid leukemia (AML) known as leukemic stem cells (LSC). Beyond its molecular heterogeneity, AML is also characterized by rewiring biological processes to support its onset and maintenance.

LSC were observed to inherently and actively trigger mitochondrial turnover through selective autophagic removal such that impairing the process led to cell differentiation at the expense of its stemness.

This review provides a current take on autophagy regulation mechanisms according to the current molecular characterization of the process; describes autophagy as a drug resistance mechanism, and a pivotal mechanism whereby LSC harmonize their strong reliance on mitochondrial respiration to obtain energy, and their necessity for lower internal oxidative stress to avoid exhaustion. Therefore, targeting autophagy presents a promising strategy to promote long-term remissions in AML.

造血干细胞逐渐获得遗传和表观遗传学干扰，赋予其恶性特征，使其成为新发急性髓性白血病（AML）的创始细胞和储库细胞，即白血病干细胞（LSC）。除了分子异质性外，急性髓细胞白血病还具有重构生物过程以支持其发病和维持的特点。据观察，白血病干细胞通过选择性自噬清除，固有地、主动地触发线粒体周转，因此损害这一过程会导致细胞分化，牺牲细胞的干性。本综述根据目前自噬过程的分子特征，对自噬调控机制进行了分析；将自噬描述为一种耐药机制，也是一种关键机制，LSC 可借此协调其对线粒体呼吸获取能量的强烈依赖和降低内部氧化应激以避免衰竭的必要性。因此，以自噬为靶点是促进急性髓细胞性白血病长期缓解的一种有前景的策略。

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引用次数: 0

Targeting extracellular matrix interaction in gastrointestinal cancer: Immune modulation, metabolic reprogramming, and therapeutic strategies 针对胃肠道癌症中细胞外基质的相互作用：免疫调节、代谢重编程和治疗策略。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189225

Jiyifan Li , Wenxin Zhang , Lu Chen , Xinhai Wang , Jiafeng Liu , Yuxin Huang , Huijie Qi , Li Chen , Tianxiao Wang , Qunyi Li

The extracellular matrix (ECM) is a major constituent of the tumor microenvironment, acting as a mediator that supports the progression of gastrointestinal (GI) cancers, particularly in mesenchymal subtypes. Beyond providing structural support, the ECM actively shapes the tumor microenvironment (TME) through complex biochemical and biomechanical remodeling. Dysregulation of ECM composition and signaling is closely linked to increased cancer aggressiveness, poor prognosis, and resistance to therapy. ECM components, such as collagen, fibronectin, laminin, and periostin, influence tumor growth, metastasis, immune modulation, and metabolic reprogramming by interacting with tumor cells, immune cells, and cancer-associated fibroblasts. In this review, we highlight the heterogeneous nature of the ECM and the dualistic roles of its components across GI cancers, with a focus on their contributions to immune evasion and metabolic remodeling via intercellular interactions. Additionally, we explore therapeutic strategies targeting ECM remodeling and ECM-centered interactions, emphasizing their potential in enhancing existing anti-tumor therapies.

细胞外基质（ECM）是肿瘤微环境的主要成分，是支持胃肠道癌症（尤其是间质亚型癌症）进展的介质。除了提供结构支持外，ECM 还通过复杂的生化和生物力学重塑积极塑造肿瘤微环境 (TME)。ECM 成分和信号传导失调与癌症侵袭性增加、预后不良和耐药性密切相关。ECM 成分（如胶原蛋白、纤连蛋白、层粘连蛋白和骨膜粘连蛋白）通过与肿瘤细胞、免疫细胞和癌症相关成纤维细胞相互作用，影响肿瘤的生长、转移、免疫调节和代谢重编程。在这篇综述中，我们强调了 ECM 的异质性及其成分在消化道癌症中的双重作用，重点是它们通过细胞间相互作用对免疫逃避和代谢重塑的贡献。此外，我们还探讨了针对 ECM 重塑和以 ECM 为中心的相互作用的治疗策略，强调它们在增强现有抗肿瘤疗法方面的潜力。

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引用次数: 0

Advances of SS18-SSX fusion gene in synovial sarcoma: Emerging novel functions and therapeutic potentials 滑膜肉瘤中 SS18-SSX 融合基因的研究进展：新功能和治疗潜力。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189215

Chongmin Ren , Jia Liu , Francis J. Hornicek , Bin Yue , Zhenfeng Duan

Synovial sarcoma is a rare type of soft tissue sarcoma that primarily affects adolescents and young adults, featured by aggressive behavior and a high potential for metastasis. Genetically, synovial sarcoma is defined by the fusion oncogene SS18-SSX arising from the translocation of t(X;18)(p11;q11). SS18-SSX fusion gene is the major driver of the oncogenic event in synovial sarcoma. SS18-SSX fusion protein, while not containing any DNA-binding motifs, binds to the SWI/SNF (BAF) complex, a major epigenetic regulator, leading to the disruption of gene expression which results in tumor initiation and progression. Emerging studies on the molecular mechanisms of SS18-SSX associated signaling pathway hold promise for developments in diagnosis and treatments. Advanced diagnostic methods facilitate early and precise detection of the tumor, enabling disease monitoring and prognostic improvements. Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.

滑膜肉瘤是一种罕见的软组织肉瘤，主要累及青少年和年轻人，具有侵袭性和高度转移性。从遗传学角度看，滑膜肉瘤是由 t(X;18)(p11;q11)易位产生的融合癌基因 SS18-SSX 确定的。SS18-SSX 融合基因是滑膜肉瘤致癌事件的主要驱动因素。SS18-SSX 融合蛋白虽然不含任何 DNA 结合基团，却能与 SWI/SNF （BAF）复合物（一种主要的表观遗传调节因子）结合，导致基因表达紊乱，从而导致肿瘤的发生和发展。有关 SS18-SSX 信号通路分子机制的新研究为诊断和治疗带来了希望。先进的诊断方法有助于早期精确检测肿瘤，从而实现疾病监测和改善预后。滑膜肉瘤的治疗通常包括局部手术、放疗和化疗，同时也在探索免疫疗法、靶向疗法和表观遗传修饰剂等新型治疗方法。本综述重点介绍 SS18-SSX 融合基因、表观遗传格局、信号通路、诊断技术和相关治疗进展的最新研究，旨在抑制致癌过程，改善滑膜肉瘤患者的预后。

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引用次数: 0

Developing pioneering pharmacological strategies with CRISPR/Cas9 library screening to overcome cancer drug resistance 利用 CRISPR/Cas9 文库筛选技术开发开创性药理学策略，克服癌症抗药性。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189212

Yu He , Huan Li , Xueming Ju , Bo Gong

Cancer drug resistance is a major obstacle to the effectiveness of chemoradiotherapy, targeted therapy, and immunotherapy. CRISPR/Cas9 library screening has emerged as a powerful genetic screening tool with significant potential to address this challenge. This review provides an overview of the development, methodologies, and applications of CRISPR/Cas9 library screening in the study of cancer drug resistance. We explore its role in elucidating resistance mechanisms, identifying novel anticancer targets, and optimizing treatment strategies. The use of in vivo single-cell CRISPR screens is also highlighted for their capacity to reveal T-cell regulatory networks in cancer immunotherapy. Challenges in clinical translation are discussed, including off-target effects, complexities in data interpretation, and model selection. Despite these obstacles, continuous technological advancements indicate a promising future for CRISPR/Cas9 library screening in overcoming cancer drug resistance.

癌症耐药性是化放疗、靶向治疗和免疫治疗有效性的主要障碍。CRISPR/Cas9 文库筛选已成为一种强大的基因筛选工具，具有应对这一挑战的巨大潜力。本综述概述了 CRISPR/Cas9 文库筛选在癌症耐药性研究中的发展、方法和应用。我们探讨了它在阐明抗药性机制、确定新型抗癌靶点和优化治疗策略方面的作用。此外，我们还强调了体内单细胞 CRISPR 筛选在揭示癌症免疫疗法中的 T 细胞调控网络方面的作用。报告还讨论了临床转化过程中面临的挑战，包括脱靶效应、数据解读的复杂性和模型选择。尽管存在这些障碍，但技术的不断进步预示着 CRISPR/Cas9 文库筛选在克服癌症耐药性方面大有可为。

引用次数: 0

Epigenetic regulation of TGF-β and vice versa in cancers – A review on recent developments 癌症中 TGF-β 和 TGF-β 的表观遗传调控--最新进展综述。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189219

Ankit Naik, Noopur Thakur

This review explores the complex relationship between epigenetic mechanisms and Transforming Growth Factor-beta (TGF-β) signalling pathways in the field of cancer research. The study provides an overview of the latest advancements in understanding the crucial functions of epigenetic alterations, such as DNA methylation, histone modifications, and chromatin remodeling, in significantly impacting the TGF-β signalling pathway. The dynamic epigenetic modifications are essential in determining the behaviour of cancer cells, impacting the interactions with the tumor microenvironment, and affecting the overall process of carcinogenesis. Significant attention is given to Breast cancer, Lung cancer, Liver cancer, Prostate cancer, and Pancreatic cancer. Research has revealed intricate regulatory networks in these cancers, involving long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and histone post-translational modifications. These networks are closely connected to TGF-β signalling. Both findings highlight the significant interaction between epigenetic regulation and TGF-β signalling in cancer. They provide valuable insights that can guide the development of new treatment approaches to target both pathways and prevent cancer growth and metastasis.

这篇综述探讨了癌症研究领域中表观遗传机制与转化生长因子-β（TGF-β）信号通路之间的复杂关系。研究概述了在理解表观遗传学改变（如 DNA 甲基化、组蛋白修饰和染色质重塑）对 TGF-β 信号通路产生重大影响的关键功能方面取得的最新进展。动态的表观遗传修饰对决定癌细胞的行为、影响与肿瘤微环境的相互作用以及影响整个癌变过程至关重要。乳腺癌、肺癌、肝癌、前列腺癌和胰腺癌备受关注。研究揭示了这些癌症中错综复杂的调控网络，涉及长非编码 RNA（lncRNA）、microRNA（miRNA）和组蛋白翻译后修饰。这些网络与 TGF-β 信号密切相关。这两项发现都强调了表观遗传调控与 TGF-β 信号在癌症中的重要相互作用。它们提供了有价值的见解，可以指导开发新的治疗方法，针对这两种途径预防癌症的生长和转移。

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引用次数: 0

The interplay between microbiome and host factors in pathogenesis and therapy of head and neck cancer 微生物组和宿主因素在头颈癌发病和治疗中的相互作用。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189216

Martina Raudenská , Maria Bugajová , David Kalfeřt , Jan Plzák , Adam Šubrt , Petra Tesařová , Michal Masařík

Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years. This review article describes the bidirectional communication between the host and the oral/gut microbiome, focusing on microbiome-derived metabolites and their impact on systemic immune responses and the modulation of the tumour microenvironment. In addition, we review the role of host lifestyle factors in shaping the composition of the oral/gut microbiota and its impact on cancer progression and therapy. Overall, this review highlights the rationality of considering the oral/gut microbiota as a critical determinant of cancer therapy outcomes and points to therapeutic opportunities offered by targeting the oral/gut microbiota in the management of HNSCC.

头颈部鳞状细胞癌（HNSCC）等缺乏强驱动突变和高渗透性的异质性癌症，由于遗传和环境因素之间复杂的相互作用，给了解其病因学带来了独特的挑战。生活方式因素（如口腔卫生差、吸烟或饮酒）、口腔和肠道微生物组以及宿主遗传之间的相互作用在 HNSCC 中显得尤为重要。近年来，肠道微生物群与癌症治疗结果之间复杂的相互作用也受到越来越多的关注。这篇综述文章描述了宿主与口腔/肠道微生物组之间的双向交流，重点关注微生物组衍生的代谢物及其对全身免疫反应和肿瘤微环境调控的影响。此外，我们还回顾了宿主生活方式因素在塑造口腔/肠道微生物群组成中的作用及其对癌症进展和治疗的影响。总之，本综述强调了将口腔/肠道微生物群视为癌症治疗结果的关键决定因素的合理性，并指出了在 HNSCC 的治疗中针对口腔/肠道微生物群提供的治疗机会。

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引用次数: 0

Recent insights into RNA m5C methylation modification in hepatocellular carcinoma 肝细胞癌中 RNA m5C 甲基化修饰的最新研究成果。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189223

Danyang Li , Yanyan Liu , Guang Yang , Mingyu He , Ligong Lu

RNA 5-methylcytosine (m5C) methylation involves the addition of a methyl (-CH3) group to the cytosine (C) base within an RNA molecule, forming the m5C modification. m5C plays a role in numerous essential biological processes, including the regulation of RNA stability, nuclear export, and protein translation. Recent studies have highlighted the importance of m5C in the pathogenesis of various diseases, particularly tumors. Emerging evidence indicates that RNA m5C methylation is intricately implicated in the mechanisms underlying hepatocellular carcinoma (HCC). Dysregulation of m5C-associated regulatory factors is common in HCC and shows significant associations with prognosis, treatment response, and clinicopathological features. This review provides an in-depth analysis of the components and functions of m5C regulators, particularly emphasizing their research advancements in the context of HCC.

RNA 5-甲基胞嘧啶（m5C）甲基化涉及在 RNA 分子中的胞嘧啶（C）碱基上添加甲基（-CH3），形成 m5C 修饰。m5C 在许多重要的生物过程中发挥作用，包括调节 RNA 的稳定性、核输出和蛋白质翻译。最近的研究强调了 m5C 在各种疾病（尤其是肿瘤）发病机制中的重要性。越来越多的证据表明，RNA m5C 甲基化与肝细胞癌（HCC）的发病机制有着千丝万缕的联系。m5C 相关调控因子的失调在 HCC 中很常见，并与预后、治疗反应和临床病理特征有显著关联。本综述深入分析了 m5C 调节因子的组成和功能，并特别强调了它们在 HCC 方面的研究进展。

引用次数: 0

Phase separation in DNA damage response: New insights into cancer development and therapy DNA 损伤反应中的相分离：癌症发展与治疗的新视角

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-11-01 DOI: 10.1016/j.bbcan.2024.189206

Lingwei Li , Litong Yao , Mozhi Wang , Xiang Zhou , Yingying Xu

Phase separation, a process in which biomolecules segregate into distinct liquid-like compartments within cells, has recently been identified as a crucial regulator of various cellular functions, including the DNA damage response (DDR). Dysregulation of phase separation may contribute to genomic instability, oncogenesis, and tumor progression. However, the specific roles and mechanisms underlying phase separation remain largely elusive. This comprehensive review aims to elucidate the complex relationship between phase separation and the DDR in the context of cancer biology. We focus on the molecular mechanisms underlying phase separation and its role in orchestrating DDR signaling and repair processes. Additionally, we discuss how the dysregulation of phase separation in cancer cells impacts genome stability, tumorigenesis, and therapeutic responses. By leveraging the unique properties of phase separation in the DDR, researchers can potentially advance basic research and develop personalized cancer therapies targeting the dysregulated biomolecular condensates that drive tumorigenesis.

相分离是生物大分子在细胞内分离成不同液态区室的过程，最近已被确定为各种细胞功能（包括 DNA 损伤反应）的关键调节因子。相分离失调可能会导致基因组不稳定、肿瘤发生和肿瘤进展。然而，相分离的具体作用和机制在很大程度上仍然难以捉摸。本综述旨在阐明癌症生物学背景下相位分离与 DDR 之间的复杂关系。我们将重点关注相分离的分子机制及其在协调 DDR 信号传导和修复过程中的作用。此外，我们还讨论了癌细胞中的相分离失调如何影响基因组稳定性、肿瘤发生和治疗反应。通过利用 DDR 中相位分离的独特特性，研究人员有可能推进基础研究，并开发出针对导致肿瘤发生的失调生物分子凝聚物的个性化癌症疗法。

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引用次数: 0