Seminars in oncology最新文献_第4页

MicroRNAs: From bench to bedside applications as breast cancer therapsseutics microrna：从实验到临床应用，作为乳腺癌治疗药物

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-04 DOI: 10.1016/j.seminoncol.2025.152386

Md Abdus Samad , Iftikhar Ahmad , Muhammad Nadeem Asghar , Mohd Suhail , Mohd Rehan , Fahad A. Al-Abbasi , Khadeejah Alsolami , Mohd Suhail Akhter , Ausaf Ahmad , Shams Tabrez

MicroRNAs (miRNAs) or small noncoding RNA molecules, 18–22 nucleotides long, are evolutionarily conserved and may have an impact on the behavior and progression of tumors. Cancer initiation, proliferation, invasion, and metastasis are all related to the specific deregulation of miRNAs. It also affects the genes involved in metabolism, apoptosis, cellular differentiation, and proliferation. Understanding the functional roles of miRNAs could shed light on the intricate molecular mechanism that underlie cancer growth. The purpose of this review is to investigate the presence of tumor-suppressive, oncogenic, and metastatic miRNAs in cancer cells, specifically breast cancer (BC) and how these miRNAs affect the development of BC and its subtypes. In addition, the miRNA-based therapeutic strategies and utilization of different delivery system to enhance the efficacy has also been covered. Based on our article, miRNAs appear to be cutting-edge prognostic, therapeutic, and diagnostic tools for the treatment of BC. However, several barriers, such as, delivery systems, side effects, demographic variabilities, and lengthy clinical studies needs to be optimized before these miRNAs could be routinely used in clinical settings.

MicroRNAs （miRNAs）或小的非编码RNA分子，长18-22个核苷酸，是进化上保守的，可能对肿瘤的行为和进展有影响。癌症的发生、增殖、侵袭和转移都与mirna的特异性失调有关。它还影响参与代谢、凋亡、细胞分化和增殖的基因。了解mirna的功能作用可以揭示癌症生长背后复杂的分子机制。本综述的目的是研究肿瘤抑制、致癌和转移性mirna在癌细胞，特别是乳腺癌（BC）中的存在，以及这些mirna如何影响BC及其亚型的发展。此外，还介绍了基于mirna的治疗策略和利用不同的递送系统来提高疗效。根据我们的文章，mirna似乎是治疗BC的前沿预后、治疗和诊断工具。然而，在这些mirna在临床常规使用之前，还需要优化一些障碍，如递送系统、副作用、人口统计学变异和冗长的临床研究。

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引用次数: 0

Deciphering autophagy signaling in cancer: A paradigm shift from molecular classifications to clinical innovations. 解读癌症中的自噬信号：从分子分类到临床创新的范式转变。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-08-08 DOI: 10.1016/j.seminoncol.2025.152397

Farag M A Altalbawy, Ehab Yassen Theab, Gaurav Sanghvi, R Roopashree, Aditya Kashyap, Hussein Riyadh Abdul Kareem Al-Hetty, S Gayathri, Rajashree Panigrahi, Yasser Fakri Mustafa, Hatif Abdulrazaq Yasin

The intracellular breakdown process known as autophagy occurs when cells experience adverse conditions, such as organelle damage, the presence of abnormal proteins, hypoxia stress, low energy levels, or nutritional deprivation. The autophagic process begins by forming autophagosomes, which then merge with lysosomes to recycle degraded materials. Autophagy functions in multiple ways to affect cancer development and treatment outcomes. Tumor cells with low autophagy levels may exhibit anti-tumor effects during cancer initiation because their connection to malignant transformation is possible. The promotion of autophagy appears beneficial for cancer prevention in this context. The survival of cancer cells through increased autophagy enables tumor growth in existing tumors by allowing them to overcome metabolic and treatment-related challenges. Research indicates that blocking autophagy through the use of drugs or genetic methods makes cancer cells more susceptible to chemotherapy, radiation, and targeted therapies, suggesting that inhibiting the autophagic system may be a promising approach to enhance treatment. Excessive autophagy activation could be a therapeutic approach to manage cancer cells that resist cell death. The successful treatment of cancer requires an understanding of autophagy's dual nature. This review examines potential therapeutic strategies for tumors by analyzing autophagy-related signaling pathways and the essential factors that influence cancer development.

当细胞经历不利条件时，如细胞器损伤、异常蛋白的存在、缺氧应激、低能量水平或营养剥夺，细胞内分解过程即自噬发生。自噬过程始于形成自噬体，然后自噬体与溶酶体结合以回收降解物质。自噬以多种方式影响癌症的发展和治疗结果。低自噬水平的肿瘤细胞可能在癌变过程中表现出抗肿瘤作用，因为它们可能与恶性转化有关。在这种情况下，促进自噬似乎有利于预防癌症。癌细胞通过增加的自噬存活，使现有肿瘤能够克服代谢和治疗相关的挑战，从而使肿瘤生长。研究表明，通过药物或遗传方法阻断自噬使癌细胞更容易受到化疗、放疗和靶向治疗的影响，这表明抑制自噬系统可能是一种有希望的增强治疗的方法。过度自噬激活可能是一种治疗方法来管理癌细胞抵抗细胞死亡。癌症的成功治疗需要了解自噬的双重性质。本文通过分析自噬相关信号通路和影响肿瘤发展的重要因素来探讨肿瘤的潜在治疗策略。

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引用次数: 0

Metabolic reprogramming: The driving force behind cancer drug resistance 代谢重编程：癌症耐药性背后的驱动力

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-16 DOI: 10.1016/j.seminoncol.2025.152392

Amr Ali Mohamed Abdelgawwad El-Sehrawy , Chou-Yi Hsu , Ali G. Alkhathami , Muktesh Chandra , Tina Saeed Basunduwah , H. Malathi , Jitendra Narayan Senapati , Apurav Gautam , Mundher Kadhem , Hatif Abdulrazaq Yasin

Metabolic reprogramming enables stress adaptation of cancer cells to treatment and is a primary causative force of drug resistance. Dysregulation of glucose, amino acid, and lipid metabolism supplies energy, biosynthetic precursors, and redox balance, promoting survival in the treated tumor. These processes are coordinated by oncogenic signaling, loss of tumor suppressors, and regulatory non-coding RNAs, which promote cancer stemness, immune evasion, and resistance to apoptosis. This review examines the mechanisms by which central metabolic pathways, particularly glycolysis, glutamine metabolism, and fatty acid synthesis, are altered to facilitate drug resistance in various types of cancer. Additionally, we report on novel therapeutic approaches that exploit such metabolic weaknesses to prevent therapy resistance and enhance clinical outcomes. Future directions emphasize the need for advanced metabolic profiling to personalize treatment approaches and the clinical translation of promising preclinical findings to overcome this significant obstacle in cancer therapy.

代谢重编程使癌细胞能够适应治疗的压力，是耐药性的主要致病力。葡萄糖、氨基酸和脂质代谢失调提供能量、生物合成前体和氧化还原平衡，促进治疗肿瘤的生存。这些过程是由致癌信号、肿瘤抑制因子的缺失和调节非编码rna协调的，这些非编码rna促进癌症的发生、免疫逃避和对细胞凋亡的抵抗。这篇综述探讨了中枢代谢途径，特别是糖酵解、谷氨酰胺代谢和脂肪酸合成被改变以促进各种类型癌症耐药的机制。此外，我们报告了利用这种代谢弱点来预防治疗耐药性和提高临床结果的新治疗方法。未来的方向强调需要先进的代谢分析来个性化治疗方法和临床前研究结果的临床转化，以克服癌症治疗中的这一重大障碍。

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引用次数: 0

Clinical efficacy and security analysis of DEB-TACE combined with trans arterial infusion of carrelizumab in the therapy of advanced liver cancer DEB-TACE联合经动脉输注卡瑞珠单抗治疗晚期肝癌的临床疗效及安全性分析

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-17 DOI: 10.1016/j.seminoncol.2025.152393

Yang Chen, Xinxin Zang, Xiaoxuan Zhang, Songyan Zhang

To explore the clinical efficacy and security analysis of DEB-TACE combined with carrelizumab in the therapy of advanced liver cancer. This study was prospectively designed. Using a random number table method, 96 patients with advanced liver cancer hospitalized from August 2022 to August 2023 were divided into the DT group (DEB-TACE treatment, n = 48) and the DT-C group (on the basis of the DT group, receiving carrelizumab infusion via hepatic artery, n = 48). The changes of therapeutic effect, serum tumor markers, T lymphocyte subsets, overall survival (OS) and progression-free survival (PFS) and the adverse effect were observed. The ORR and DCR of the DT-C group were higher than that of the DT group (P < 0.05). After 1 month of treatment, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ were increased and the DT-C group was higher than the DT group (P < 0.001). The CD8+ decreased after 1 month of treatment, and the CD8+ in the DT-C group was significantly lower than that in the DT group (P < 0.001). AFP and PIVKA-II decreased after 1 month of treatment, and the DT-C group was lower than the DT group (P < 0.001). The overall survival (OS) (2-year survival rate 33.33%) and progression-free survival (PFS) (2-year survival rate 18.75%) of the DT-C group were higher than those of the DT group (P < 0.05). There was no difference in the adverse reaction incidence (P > 0.05). DEB-TACE combined with trans arterial infusion of carrelizumab is safe and effective in the treatment of advanced liver cancer. Compared with DEB-TACE alone, this combination therapy results in higher CD3+, CD4+, and CD4+/CD8+ levels, as well as reduced CD8+, AFP, and PIVKA-II levels.

探讨DEB-TACE联合卡瑞珠单抗治疗晚期肝癌的临床疗效及安全性分析。本研究采用前瞻性设计。采用随机数字表法，将2022年8月至2023年8月住院的96例晚期肝癌患者分为DT组（DEB-TACE治疗，n = 48）和DT- c组（在DT组的基础上，经肝动脉输注卡瑞珠单抗，n = 48）。观察两组治疗效果、血清肿瘤标志物、T淋巴细胞亚群、总生存期（OS）、无进展生存期（PFS）及不良反应的变化。DT- c组的ORR和DCR均高于DT组（P <； 0.05）。治疗1个月后CD3+、CD4+、CD4+/CD8+均升高，且DT- c组高于DT组（P <； 0.001）。治疗1个月后CD8+下降，DT- c组CD8+明显低于DT组（P <； 0.001）。治疗1个月后，AFP和PIVKA-II降低，DT- c组低于DT组（P <； 0.001）。DT- c组总生存率（OS）（2年生存率33.33%）和无进展生存率（PFS）（2年生存率18.75%）均高于DT组（P <； 0.05）。两组不良反应发生率比较差异无统计学意义（P >； 0.05）。DEB-TACE联合经动脉输注卡瑞珠单抗治疗晚期肝癌安全有效。与单独使用DEB-TACE相比，这种联合治疗导致CD3+、CD4+和CD4+/CD8+水平升高，CD8+、AFP和PIVKA-II水平降低。

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引用次数: 0

Deregulated cell cycle control: The interplay between non-coding RNAs and cyclin-dependent kinases in tumorigenesis 细胞周期失控：非编码rna和周期蛋白依赖性激酶在肿瘤发生中的相互作用

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-08-12 DOI: 10.1016/j.seminoncol.2025.152395

Chou-Yi Hsu , Yasir Qasim Almajidi , Maher abdulrazzaq Al-hakeem , Mohammad Y. Alshahrani , Wael Nabil , Sujayaraj Samuel Jayakumar , Siya SinglaI , Zahraa Abbas Al-Khafaji , Ahmed Remthan Hussein , Zuhair I. Al-Mashhadani

Cyclin-dependent kinases (CDKs) are a group of serine/threonine kinases that are at the center of cell cycle progression. Dysregulated CDK activity, found in a range of human cancers, leads to uncontrolled cell growth and development. Non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are emerging as critical regulators of gene expression and cellular processes, playing an important and often complex role in cancer development and progression. The purpose of this review is to organize knowledge about the interactions of ncRNAs with CDKs, contribution to cancer biology, and to discuss not only the different ways miRNAs target and downregulate CDKs mRNA, leading to inhibition of cell cycle progression and acting as tumor suppressors, but in the case of some miRNAs alter CDK activity as oncogenes by directly upregulating CDK expression or more frequently suppressing the expression of the canonical CDK inhibitors (p21 and p27). Moreover, long non-coding RNAs (lncRNAs) can regulate CDKs through a variety of mechanisms, such as functioning as molecular sponges by absorbing miRNAs that target CDK proteins as miRNA sponges, modulating CDK protein abundance and/or activity indirectly or directly (i.e., the direct interaction with the CDK proteins can potentially invoke an ability to regulate their stability, etc.). Circulating RNAs (circRNAs) also primarily modulate CDK levels and act as inhibitors of the appropriate CDK targeted by a miRNA sponge, potentially through direct interaction with a CDK. Overall, while our understanding of the ncRNA-CDK network is far from complete, the complexities surrounding ncRNA-CDK oncogenic developments and the ability to target these pathways offer significant promise in the harsh realities of cancerogenesis and further therapeutic interventions to fashion more precise cancer therapies that antagonize aberrant cell cycle progression in cancer subtypes.

细胞周期蛋白依赖性激酶（CDKs）是一组丝氨酸/苏氨酸激酶，处于细胞周期进程的中心。在一系列人类癌症中发现的CDK活性失调会导致细胞生长和发育失控。非编码rna (ncRNAs)，包括微rna （miRNAs）、长链非编码rna （lncRNAs）和环状rna (circRNAs)，正在成为基因表达和细胞过程的关键调节因子，在癌症的发生和进展中发挥着重要而复杂的作用。本综述的目的是组织有关ncRNAs与CDKs相互作用的知识，对癌症生物学的贡献，并不仅讨论miRNAs靶向和下调CDKs mRNA的不同方式，导致细胞周期进程的抑制和肿瘤抑制，而且在一些miRNAs通过直接上调CDK表达或更频繁地抑制典型CDK抑制剂的表达来改变CDK活性作为癌基因（p21和p27）。此外，长链非编码rna （lncRNAs）可以通过多种机制调节CDKs，例如通过吸收靶向CDK蛋白的miRNA作为miRNA海绵发挥分子海绵的作用，间接或直接调节CDK蛋白的丰度和/或活性（即，与CDK蛋白的直接相互作用可以潜在地调用调节其稳定性的能力等）。循环rna （circRNAs）也主要调节CDK水平，并作为miRNA海绵靶向的适当CDK的抑制剂，可能通过与CDK的直接相互作用。总的来说，虽然我们对ncRNA-CDK网络的理解还远未完成，但围绕ncRNA-CDK致癌发展的复杂性和靶向这些途径的能力为癌症发生的残酷现实和进一步的治疗干预提供了重要的希望，以形成更精确的癌症治疗方法，对抗癌症亚型中异常的细胞周期进展。

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引用次数: 0

Psoas muscle depletion correlates with poor prognosis and compromised immunity in resectable gastric cancer: A multicenter study 腰肌耗竭与可切除胃癌预后不良和免疫功能低下相关：一项多中心研究

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-08-11 DOI: 10.1016/j.seminoncol.2025.152400

Hao Zhou , Li Zhong , Zihan Jin , Xun Hou , Haiyun Tang , Shibin Yang , Yulong He , Wu Song , Changhua Zhang , Zhewei Wei

Sarcopenia, assessed by the psoas muscle index (PMI), is characterized with the loss of skeletal muscle mass and strength, and has gained growing attentions in the field of cancers. However, its role in gastric cancer (GC), especially in patients received gastrectomy, remains underexplored. This multicenter retrospective study examined 439 patients with resectable GC to assess the prognostic significance of sarcopenia, measured by PMI and PMI change rate (PMICR), while also exploring potential links with tumor immunity. Kaplan–Meier analysis revealed that low PMICR was significantly associated with worse survival outcomes in all patient cohorts. Further multivariate Cox analysis identified PMICR (hazard ratio: 2.80, 95% CI: 1.73–4.56), but not baseline PMI—as an independent predictor of overall survival. Immunologically, low PMICR patients exhibited decreased tertiary lymphoid structure density and reduced tumor-infiltrating lymphocytes (CD3+ T cells and CD20+ B cells). The developed nomogram incorporating PMICR showed superior prognostic performance versus TNM stage, with concordance indices of 0.821 (95% CI: 0.789–0.853), 0.800 (95% CI: 0.753–0.847), and 0.816 (95% CI: 0.743–0.889) for training, internal validation, and external validation cohorts, respectively. These results suggested that PMICR, as a measure of sarcopenia, more accurately predicted survival outcomes and might be associated with immune status in resectable GC patients. Moreover, the newly developed nomogram demonstrated high accuracy in predicting prognosis.

以腰肌指数（PMI）评估的骨骼肌减少症以骨骼肌质量和力量的减少为特征，在癌症领域受到越来越多的关注。然而，其在胃癌（GC）中的作用，特别是在接受胃切除术的患者中，仍未得到充分探讨。这项多中心回顾性研究检查了439例可切除的胃癌患者，通过PMI和PMI变化率（PMICR）来评估肌肉减少症的预后意义，同时也探索了与肿瘤免疫的潜在联系。Kaplan-Meier分析显示，在所有患者队列中，低PMICR与较差的生存结果显著相关。进一步的多变量Cox分析确定PMICR（风险比：2.80,95% CI: 1.73-4.56）是总生存期的独立预测因子，但不是基线pmi。在免疫学上，低PMICR患者表现出三级淋巴结构密度降低和肿瘤浸润淋巴细胞（CD3+ T细胞和CD20+ B细胞）减少。与TNM分期相比，纳入PMICR的nomogram显示出更好的预后表现，训练组、内部验证组和外部验证组的一致性指数分别为0.821 （95% CI: 0.789-0.853）、0.800 （95% CI: 0.753-0.847）和0.816 （95% CI: 0.743-0.889）。这些结果表明，PMICR作为肌肉减少症的一种测量方法，更准确地预测了可切除胃癌患者的生存结果，并可能与免疫状态相关。此外，新开发的nomogram预测预后的准确度较高。

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引用次数: 0

Application prospects of tumor vaccines for pancreatic cancer: From TAAs to TSAs and combination strategies 胰腺癌肿瘤疫苗的应用前景：从TAAs到TSAs及联合策略

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1016/j.seminoncol.2025.152399

Zerui Lu , Wenxin Zhu , Xinjian Liu

Pancreatic cancer, a highly aggressive malignancy of the digestive system, exhibits therapeutic resistance due to its immunosuppressive tumor microenvironment (TME) and early metastatic potential. Cancer vaccines targeting tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs) have emerged as promising immunotherapeutic strategies. TAA-based vaccines demonstrate T cell activation and tumor suppression in preclinical models, yet face limitations from antigen heterogeneity and immunosuppressive TME. TSA-directed vaccines, exemplified by personalized mRNA vaccines incorporating whole-exome sequencing-selected neoantigens, achieved long-term recurrence-free survival in 50% of vaccinated patients during phase I/II trials, with phase III data supporting synergistic efficacy when combined with chemotherapy and programmed death receptor 1 (PD-1) inhibitors. KRAS-targeted vaccines address common mutations (e.g., G12D, G12V) to broaden applicability. This review presents an updated summary of current tumor vaccine types, mechanisms, and clinical implications, while analyzing how combination therapies remodel TME infiltration and reverse T cell exhaustion to significantly improve survival outcomes. The discussion also addresses existing challenges and proposes future directions in pancreatic cancer vaccine development.

胰腺癌是一种高度侵袭性的消化系统恶性肿瘤，由于其免疫抑制肿瘤微环境（TME）和早期转移潜力而表现出治疗耐药性。针对肿瘤相关抗原（TAAs）或肿瘤特异性抗原（TSAs）的癌症疫苗已成为有前途的免疫治疗策略。基于taa的疫苗在临床前模型中显示出T细胞活化和肿瘤抑制，但面临抗原异质性和免疫抑制TME的限制。tsa导向疫苗，以结合全外显子组测序选择的新抗原的个性化mRNA疫苗为例，在I/II期试验中，50%接种疫苗的患者实现了长期无复发生存，III期数据支持与化疗和程序性死亡受体1 （PD-1）抑制剂联合使用时的协同效果。针对kras的疫苗针对常见突变（例如G12D、G12V），以扩大适用性。本文综述了当前肿瘤疫苗类型、机制和临床意义的最新总结，同时分析了联合治疗如何重塑TME浸润和逆转T细胞衰竭以显着改善生存结果。讨论还涉及现有的挑战，并提出胰腺癌疫苗开发的未来方向。

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引用次数: 0

Multiple myeloma: Insights into underlying mechanisms, advances in diagnostic and therapeutic modalities 多发性骨髓瘤：对潜在机制的洞察，诊断和治疗方式的进展

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-10 DOI: 10.1016/j.seminoncol.2025.152390

Rohitash Yadav , Jitendra Kumar Chaudary , Khushboo Bisht , Puneet Dhamija , Pankaj Kumar Chaudhary , Uttam Kumar Nath , Neeraj Jain

Multiple myeloma (MM) is characterized by malignant proliferation and accumulation of terminally differentiated antibody-producing plasma cells in bone marrow. The underlying genetic causes of MM are highly complex, involving the loss of function in a myriad of crucial genes, especially those involved in DNA replication fidelity and repair. The important genetic events underscoring MM mutagenesis entail large-scale chromosomal aberrations, localized genetic changes, defective DNA repair mechanisms, point mutation, and mutagenic activity of enzymes such as activation-induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, and catalytic polypeptide (APOBEC). Despite considerable improvement in treatment regimen, MM disease remains incurable for majority of patients with very high mortality. Notably, delay in diagnosis of MM could indirectly contribute to the worse clinical outcomes and lower treatment responsiveness through several mechanisms. Primarily, MM diagnosis relies on histopathological changes and molecular profiling of the patient’s sample. In the past decades, new methods of MM diagnosis and therapeutic approaches have been invented. Together, advances in disease understanding, diagnosis, and novel effective therapeutic interventions have substantially helped slow down and/or arresting the disease progression in the large number of patients, thereby increasing overall survival. This review discusses the genetic causes of MM, clinical presentation, advances in diagnosis, and new therapeutic interventions, including combinations of effective agents targeting relapse/refractory MM.

多发性骨髓瘤（MM）的特点是骨髓中产生抗体的终末分化浆细胞的恶性增殖和积累。MM的潜在遗传原因非常复杂，涉及无数关键基因的功能丧失，特别是那些涉及DNA复制保真度和修复的基因。强调MM突变的重要遗传事件包括大规模染色体畸变、局部遗传改变、DNA修复机制缺陷、点突变以及激活诱导脱氨酶（AID）、载脂蛋白B mRNA编辑酶和催化多肽（APOBEC）等酶的致突变活性。尽管治疗方案有了很大的改善，但MM病对大多数患者来说仍然是无法治愈的，死亡率很高。值得注意的是，MM的诊断延迟可能通过多种机制间接导致临床结果恶化和治疗反应性降低。MM的诊断主要依赖于患者样本的组织病理学变化和分子谱。在过去的几十年里，MM的诊断和治疗方法的新方法已经发明。总之，疾病认识、诊断和新的有效治疗干预措施的进步，极大地帮助减缓和/或阻止了大量患者的疾病进展，从而提高了总生存率。本文综述了MM的遗传原因、临床表现、诊断进展和新的治疗干预措施，包括针对复发/难治性MM的有效药物组合。

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引用次数: 0

Deciphering the prognostic value and immunotherapeutic strategy of aggrephagy in melanoma: Integrating single-cell sequencing and machine learning 解读黑色素瘤的预后价值和免疫治疗策略：整合单细胞测序和机器学习

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI: 10.1016/j.seminoncol.2025.152371

Zihao Li , Jiaheng Xie , Liqun Li , Yucang He , Wanying Chen , Hao Dai , Songyun Zhao

This study aimed to investigate the role of aggrephagy in cutaneous melanoma (CM) and explore its potential as a biomarker for prognosis and therapeutic targeting. We utilized single-cell sequencing technology and machine learning algorithms to analyze melanoma transcriptome data from the TCGA database and validated our findings using 3 independent datasets from the GEO database. By employing enrichment scoring in single-cell sequencing, we identified characteristic expression patterns of different cell types involved in aggrephagy and constructed an aggrephagy-related signature (ARS). We further evaluated the association of ARS with clinical features, immune cell infiltration, tumor mutational load (TMB), and immune checkpoint gene expression. Additionally, we conducted in vivo experiments by knocking down TPX2, the most critical oncogene in ARS, using shRNA and assessed its effects on tumor proliferation and T-cell growth via subcutaneous tumor formation assays and flow cytometry in mice. The ARS demonstrated robust prognostic predictive power across multiple datasets, with higher ARS scores associated with poorer overall survival (OS) and lower levels of immune cell infiltration. Patients with low ARS scores were more likely to benefit from immune checkpoint inhibitor therapies, while those with high scores exhibited increased sensitivity to 2 common chemotherapeutic agents. Compared to published melanoma prognostic models, our ARS showed higher accuracy and stability. The construction of an ARS-related nomogram further facilitated more accurate clinical decision-making. In vivo experiments confirmed that TPX2 knockdown inhibited tumor proliferation and enhanced T-cell growth, highlighting its critical role in CM progression. Our study highlights the complex functions of the aggrephagy-related signature in cutaneous melanoma, underscoring its potential as a therapeutic target and a valuable tool for prognostic assessment.

本研究旨在探讨聚集性在皮肤黑色素瘤（CM）中的作用，并探讨其作为预后和治疗靶向的生物标志物的潜力。我们利用单细胞测序技术和机器学习算法分析来自TCGA数据库的黑色素瘤转录组数据，并使用来自GEO数据库的3个独立数据集验证我们的发现。通过在单细胞测序中使用富集评分，我们确定了不同细胞类型参与聚合的特征表达模式，并构建了聚合相关特征（ARS）。我们进一步评估了ARS与临床特征、免疫细胞浸润、肿瘤突变负荷（TMB）和免疫检查点基因表达的关系。此外，我们利用shRNA进行了体内实验，通过敲除ARS中最关键的致癌基因TPX2，并通过小鼠皮下肿瘤形成实验和流式细胞术评估了其对肿瘤增殖和t细胞生长的影响。ARS在多个数据集中显示出强大的预后预测能力，较高的ARS评分与较差的总生存率（OS）和较低的免疫细胞浸润水平相关。ARS评分低的患者更有可能受益于免疫检查点抑制剂治疗，而评分高的患者对两种常见化疗药物的敏感性增加。与已发表的黑色素瘤预后模型相比，我们的ARS显示出更高的准确性和稳定性。构建与急性呼吸道综合征相关的nomogram图，进一步提高了临床决策的准确性。体内实验证实，TPX2敲低抑制肿瘤增殖，增强t细胞生长，突出其在CM进展中的关键作用。我们的研究强调了皮肤黑色素瘤中聚集相关特征的复杂功能，强调了其作为治疗靶点和预后评估的有价值工具的潜力。

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引用次数: 0

From tissue architecture to clinical insights: Spatial transcriptomics in solid tumor studies 从组织结构到临床洞察：实体肿瘤研究中的空间转录组学

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-10-01 Epub Date: 2025-07-14 DOI: 10.1016/j.seminoncol.2025.152389

Arpit Sharma , Shruti S. Raut , Alok Shukla , Shivani Gupta , Abha Mishra , Amit Singh

Cancer is a highly heterogeneous disease, and its diagnosis, prognosis, and therapeutic responsiveness depend not only on genetic alterations but also on the intricate organization of cells within the tumor microenvironment (TME). Spatial transcriptomics—a suite of techniques that preserves the spatial context of gene expression in intact tissue—has revolutionized our ability to decipher tumor architecture and intercellular communication. This review provides an in‐depth analysis of recent advancements in spatial transcriptomics technologies and their applications in solid tumor research. We first describe the evolution of spatial transcriptomics from early in situ hybridization methods to state‐of‐the‐art imaging‐ and sequencing‐based platforms. Next, we discuss how spatially resolved transcriptomics is transforming cancer research by revealing the molecular landscapes of tumor cores, invasive edges, and immunological niches. The integration of spatial transcriptomics with single‐cell multiomics and advanced computational algorithms is leading to the identification of novel prognostic and predictive biomarkers. Despite tremendous progress, challenges remain in terms of technical resolution, data processing, sample preparation, and clinical standardization. Finally, we highlight emerging trends—including three-dimensional (3D) spatial profiling, multimodal integration, and the use of artificial intelligence and Deep learning—to envision a future in which spatial transcriptomics will serve as a pivotal tool for precision oncology. Together, these developments promise to refine cancer biomarker studies and ultimately improve patient outcomes.

癌症是一种高度异质性的疾病，其诊断、预后和治疗反应不仅取决于遗传改变，还取决于肿瘤微环境（TME）内细胞的复杂组织。空间转录组学——一套保留完整组织中基因表达空间背景的技术——已经彻底改变了我们破译肿瘤结构和细胞间通讯的能力。本文综述了空间转录组学技术的最新进展及其在实体肿瘤研究中的应用。我们首先描述了空间转录组学的演变，从早期的原位杂交方法到最先进的成像和测序平台。接下来，我们将讨论空间解析转录组学如何通过揭示肿瘤核心、侵袭边缘和免疫生态位的分子景观来改变癌症研究。空间转录组学与单细胞多组学和先进的计算算法的整合正在导致新的预后和预测性生物标志物的鉴定。尽管取得了巨大的进步，但在技术解决、数据处理、样品制备和临床标准化方面仍然存在挑战。最后，我们强调了新兴趋势-包括三维（3D）空间分析，多模式集成以及人工智能和深度学习的使用-设想空间转录组学将作为精确肿瘤学的关键工具的未来。总之，这些进展有望改进癌症生物标志物研究，并最终改善患者的治疗效果。

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引用次数: 0