Seminars in oncology最新文献_第5页

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 : 2025-07-14 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

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 : 2025-07-10 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

LncRNA THUMPD3-AS1 promotes the proliferation and migration of esophageal cancer cells through the miR-29a-3p/ELK1/PRDX4 signaling pathway LncRNA THUMPD3-AS1通过miR-29a-3p/ELK1/PRDX4信号通路促进食管癌细胞的增殖和迁移

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-09 DOI: 10.1016/j.seminoncol.2025.152350

Mingming Tang , Jianjun Sun , Zhigang Cai

Esophageal cancer (ESCA) is a significant contributor to cancer-related deaths worldwide due to its aggressive nature and poor prognosis. Recent research indicates that non-coding RNAs are critical in tumor progression. This study intends to explore the interaction between LncRNA THUMPD3-AS1 and miR-29a-3p in ESCA advancement. By conducting bioinformatic analyses and validating differentially expressed genes in ESCA clinical samples, the regulatory relationship between THUMPD3-AS1, miR-29a-3p, ETS transcription factor (ELK1), and Peroxiredoxin 4 (PRDX4) was investigated using various functional assays. In vitro and in vivo experiments were also carried out to assess the impact of this interaction on tumor growth and ESCA progression. Results indicated elevated levels of THUMPD3-AS1 in ESCA tissues, acting as a sponge for miR-29a-3p, a microRNA known for its tumor-suppressive properties. This interaction relieved miR-29a-3p's inhibition of ELK1, resulting in increased PRDX4 expression. Functional tests confirmed that the THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4 axis supports tumor proliferation, migration, and invasion in ESCA. Further validation of these findings was done through in vivo experiments. In conclusion, this study underscores the significance of the THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4 axis as a crucial regulatory pathway in ESCA, unveiling its oncogenic role in enhancing tumor aggressiveness.

食管癌（ESCA）由于其侵袭性和预后差，是全球癌症相关死亡的重要原因。最近的研究表明，非编码rna在肿瘤进展中起着至关重要的作用。本研究旨在探讨LncRNA THUMPD3-AS1与miR-29a-3p在ESCA进展中的相互作用。通过对ESCA临床样本进行生物信息学分析和差异表达基因验证，利用各种功能分析研究了THUMPD3-AS1、miR-29a-3p、ETS转录因子（ELK1）和过氧化物还氧蛋白4 （PRDX4）之间的调控关系。体外和体内实验也进行了评估这种相互作用对肿瘤生长和ESCA进展的影响。结果表明，ESCA组织中THUMPD3-AS1水平升高，充当miR-29a-3p的海绵，miR-29a-3p是一种以其肿瘤抑制特性而闻名的microRNA。这种相互作用减轻了miR-29a-3p对ELK1的抑制，导致PRDX4表达增加。功能测试证实，THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4轴支持ESCA中肿瘤的增殖、迁移和侵袭。通过体内实验进一步验证了这些发现。总之，本研究强调了THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4轴在ESCA中作为一个重要的调控通路的重要性，揭示了其在增强肿瘤侵袭性中的致癌作用。

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引用次数: 0

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 : 2025-07-04 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

Baicalein and baicalin in cancer therapy: Multifaceted mechanisms, preclinical evidence, and translational challenges 黄芩素和黄芩苷在癌症治疗中的作用：多方面的机制、临床前证据和转化挑战

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-03 DOI: 10.1016/j.seminoncol.2025.152377

Xavier Capó , Rajesh Kumar , Abhay Prakash Mishra , Manisha Nigam , Neti Waranuch , Miquel Martorell , Farukh Sharopov , Daniela Calina , Dragoș Popa , William N. Setzer , Javad Sharifi-Rad , Raffaele Pezzani

Natural compounds with multitargeted actions are gaining prominence in oncology for their potential to complement and transcend the limitations of conventional therapies. Among them, baicalein and baicalin, two flavonoids primarily isolated from Scutellaria baicalensis, have attracted attention for their broad-spectrum anticancer properties. This review synthesizes current evidence from cellular systems, animal models, and early-phase clinical studies, exploring their pharmacological potential and translational relevance. Both molecules interfere with key hallmarks of cancer, including proliferation, survival, angiogenesis, metastasis, and immune evasion. Mechanistically, they modulate interconnected signaling cascades governing apoptosis, inflammation, and cell cycle control, and they enhance tumor sensitivity to chemotherapy and radiotherapy. In-vivo models consistently demonstrate tumor growth inhibition, while clinical data suggest a favorable safety profile, even at relatively high oral doses. However, their clinical translation remains hampered by limited solubility, poor oral bioavailability, and rapid metabolism, factors that continue to constrain their therapeutic window. Efforts to overcome these barriers through structural modification, encapsulation strategies, and advanced delivery systems are underway, yet few have advanced beyond preclinical validation. Despite these pharmacokinetic limitations, baicalein and baicalin remain compelling candidates for integrative oncological approaches. Their pleiotropic mechanisms, combined with low toxicity and synergistic behavior with standard therapies, position them as prototypes for a new generation of phytochemical-based anticancer agents. Continued work is needed to resolve formulation challenges and define precise molecular targets, but their trajectory reflects the growing scientific and clinical momentum around rationally designed natural compound therapeutics.

具有多靶点作用的天然化合物在肿瘤学中越来越突出，因为它们具有补充和超越传统治疗局限性的潜力。其中黄芩苷（baicalein）和黄芩苷（baicalin）是主要从黄芩中分离得到的两种黄酮类化合物，因其广谱抗癌特性而备受关注。这篇综述综合了目前来自细胞系统、动物模型和早期临床研究的证据，探索了它们的药理潜力和翻译相关性。这两种分子都会干扰癌症的关键特征，包括增殖、存活、血管生成、转移和免疫逃逸。在机制上，它们调节相互关联的信号级联，控制细胞凋亡、炎症和细胞周期控制，并增强肿瘤对化疗和放疗的敏感性。体内模型一致显示肿瘤生长抑制，而临床数据显示良好的安全性，即使在相对较高的口服剂量。然而，它们的临床转化仍然受到溶解度有限、口服生物利用度差和快速代谢等因素的阻碍，这些因素继续限制它们的治疗窗口期。通过结构修改、封装策略和先进的给药系统来克服这些障碍的努力正在进行中，但很少有超过临床前验证的进展。尽管存在这些药代动力学的局限性，黄芩苷和黄芩苷仍然是综合肿瘤学方法的有力候选者。它们的多效性机制，加上低毒性和与标准疗法的协同作用，使它们成为新一代基于植物化学的抗癌药物的原型。需要继续开展工作来解决配方挑战和确定精确的分子靶点，但它们的发展轨迹反映了围绕合理设计天然化合物疗法的科学和临床势头的增长。

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引用次数: 0

Breaking barriers: Deciphering the mechanisms of Olaparib resistance in prostate cancer 突破障碍：解读前列腺癌奥拉帕尼耐药机制

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-26 DOI: 10.1016/j.seminoncol.2025.152375

Amr Ali Mohammed Abdelgawwad Wl-Sehrawy , Mahmood Yaseen Mukhlif , Aysar Ashour Khalaf , Subasini Uthirapathy , Suhas Ballal , Abhayveer Singh , V. Kavitha , Laxmidhar Maharana , Hayder Ridha-Salman , Ahmed Remthan Hussein Al-Altememe

A poly (ADP-ribose) polymerase (PARP) inhibitor, Olaparib has shown notable clinical effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC) with DNA damage repair gene mutations. Though initial reactions were encouraging, the emergence of resistance poses a major clinical problem that reduces the long-term therapeutic value for patients. This paper thoroughly investigates the molecular processes behind acquired and intrinsic resistance to Olaparib in prostate cancer (PCa). Among the several resistance routes discovered are restoration of homologous recombination (HR) repair capacity via secondary BRCA2 mutations, loss of 53BP1/REV7/Shieldin complex activity, and activation of alternative DNA repair pathways. Recent studies further imply that changes in cell cycle checkpoints and epigenetic changes could help to increase therapy resistance even more. Knowing these several resistance mechanisms helps one to create reasonable combination strategies and biomarker-driven initiatives to defeat Olaparib resistance. Among the new treatment options are combination therapies aimed at compensatory DNA repair mechanisms, cell cycle checkpoint inhibitors, epigenetic modulators, and methods tackling tumor microenvironment elements. Predictive biomarker discovery of resistance will help to guide individual treatment choice and sequential therapy optimization, hence changing clinical results for advanced PCa patients in the precision medicine age.

奥拉帕尼是一种聚adp核糖聚合酶（PARP）抑制剂，在治疗DNA损伤修复基因突变的转移性去势抵抗性前列腺癌（mCRPC）中显示出显著的临床疗效。虽然最初的反应是令人鼓舞的，但耐药性的出现构成了一个主要的临床问题，降低了患者的长期治疗价值。本文深入研究了前列腺癌（PCa）获得性和内在奥拉帕尼耐药背后的分子过程。发现的几种抗性途径包括通过继发性BRCA2突变恢复同源重组（HR）修复能力，53BP1/REV7/ shield复合物活性的丧失，以及其他DNA修复途径的激活。最近的研究进一步表明，细胞周期检查点的变化和表观遗传变化可能有助于进一步增加治疗耐药性。了解这几种耐药机制有助于制定合理的组合策略和生物标志物驱动的举措，以击败奥拉帕尼耐药。新的治疗选择包括针对补偿性DNA修复机制的联合治疗、细胞周期检查点抑制剂、表观遗传调节剂和处理肿瘤微环境因素的方法。预测耐药生物标志物的发现将有助于指导个体化治疗选择和序贯治疗优化，从而改变精准医学时代晚期PCa患者的临床结果。

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引用次数: 0

Peripheral blood CD4+CD25+ T lymphocytes and TGF-β predict the prognosis in relapsed/refractory multiple myeloma treated with daratumumab 外周血CD4+CD25+ T淋巴细胞和TGF-β预测达拉单抗治疗复发/难治性多发性骨髓瘤的预后

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-25 DOI: 10.1016/j.seminoncol.2025.152373

Hanyue Xue , Fang Wei , Ruiyang Li

For patients with relapsed/refractory multiple myeloma (R/RMM), it is indispensable to choose a combination regimen based on Daratumumab, a kind of CD38-targeting monoclonal antibody (mAb), which has prominent therapeutic advantages. However, a few patients still experienced rapid progression, and the predictors of prognosis are little known. Thus, we analyzed peripheral blood (PB) CD4⁺CD25⁺ T lymphocytes and transforming growth factor-β (TGF-β) of R/RMM patients before Daratumumab treatment, to clarify their correlation with survival. Flow cytometry (FCM) was employed to detect, analyze, and compare CD4⁺CD25⁺T lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum TGF-β. Clinical indicators were gathered and classified into quartiles. In R/RMM patients’ PB, we compared these markers between the upper and lower three quartiles. We found that CD4⁺CD25⁺ T lymphocytes (pcs/µL) and TGF-β in the PB of the R/RMM patients were higher than those of the newly diagnosed MM (NDMM) patients. Additionally, serum TGF-β of R/RMM patients was positively correlated to serum creatinine (Scr) (P < 0.05). Finally, high CD4⁺CD25⁺ T lymphocytes (pcs/µL, 95% confidence interval [CI], 4.312–7.028, P = 0.001), CD4⁺CD25⁺ T lymphocytes (%, median PFS: 5.67 months, P = 0.043), and Scr (µmol/l, 95% CI, 5.378–7.422, P = 0.005) of R/RMM patients were significantly associated with inferior progression-free survival (PFS). These results suggest that patients with R/RMM are rich in CD4⁺CD25⁺ T lymphocytes and TGF-β. Additionally, R/RMM patients with elevated CD4⁺CD25⁺ T lymphocytes, TGF-β, and Scr before the treatment of daratumumab are more likely to have a poor prognosis.

对于复发/难治性多发性骨髓瘤（R/RMM）患者，选择以靶向cd38的单克隆抗体（mAb） Daratumumab为基础的联合治疗方案是必不可少的，其治疗优势突出。然而，少数患者仍经历快速进展，预后的预测因素知之甚少。因此，我们分析了达拉单抗治疗前R/RMM患者外周血（PB） CD4+CD25+ T淋巴细胞和转化生长因子-β (TGF-β)，以阐明其与生存率的相关性。流式细胞术（FCM）检测、分析和比较CD4+CD25+T淋巴细胞。采用酶联免疫吸附法（ELISA）定量血清TGF-β。收集临床指标并按四分位数进行分类。在R/RMM患者的PB中，我们比较了上下三个四分位数之间的这些标记。我们发现R/RMM患者外周血CD4+CD25+ T淋巴细胞（pcs/µL）和TGF-β高于新诊断MM （NDMM）患者。R/RMM患者血清TGF-β与血清肌酐（Scr）呈正相关（P <； 0.05）。最后，R/RMM患者的高CD4+CD25+ T淋巴细胞（pcs/µL， 95%可信区间[CI]， 4.312-7.028, P = 0.001）、CD4+CD25+ T淋巴细胞（%，中位PFS: 5.67个月，P = 0.043）和Scr（µmol/ L, 95% CI, 5.378-7.422, P = 0.005）与较差的无进展生存期（PFS）显著相关。这些结果提示R/RMM患者CD4+CD25+ T淋巴细胞和TGF-β丰富。此外，治疗前CD4+CD25+ T淋巴细胞、TGF-β、Scr升高的R/RMM患者预后更差。

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引用次数: 0

Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment 我们到了吗？肠道菌群对癌症的诊断、预后和治疗

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-25 DOI: 10.1016/j.seminoncol.2025.152376

Carlos Ordóñez , Sara Zurita , Giuliana Ramírez , Fernanda Cordeiro , Katherine Garcia-Matamoros , Fuad Huaman-Garaicoa , Andrea Orellana-Manzano , Lorena Sandoya-Onofre , Juan Pogo , Diana Carvajal-Aldaz

Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognosis, and treatment outcomes. This review analyzes observational and interventional studies conducted with human subjects over the past 5 years, highlighting significant advancements in gut microbiota research for cancer management. Observational studies consistently demonstrated differences in gut microbial composition between cancer patients and healthy controls. Moreover, microbial diversity, particularly at the species and strain level, correlated significantly with clinical outcomes. Interventional studies showed the potential of probiotics and fecal microbiota transplantation (FMT) as adjuncts in cancer therapy by restoring microbial diversity, reducing inflammation, and alleviating chemotherapy-induced complications. Collectively, these findings suggest the gut microbiota’s potential as a tool for cancer care. Future research should focus on standardizing taxonomic-level analyses, optimizing probiotic formulations, and validating FMT/AFMT clinical protocols to fully harness the gut microbiota’s diagnostic and therapeutic capabilities in oncology.

癌症仍然是全世界死亡的主要原因之一，强调需要创新的诊断和治疗工具。肠道菌群已成为影响癌症进展、预后和治疗结果的一个因素。本综述分析了过去5年来对人类受试者进行的观察性和干预性研究，强调了肠道微生物群研究在癌症管理方面的重大进展。观察性研究一致表明，癌症患者和健康对照者之间的肠道微生物组成存在差异。此外，微生物多样性，特别是在物种和菌株水平上，与临床结果显著相关。介入性研究表明，益生菌和粪便微生物群移植（FMT）作为癌症治疗的辅助手段，可以恢复微生物多样性，减少炎症，减轻化疗引起的并发症。总的来说，这些发现表明肠道微生物群作为癌症治疗工具的潜力。未来的研究应集中在标准化分类水平分析，优化益生菌配方，验证FMT/AFMT临床方案，以充分利用肠道微生物群在肿瘤学中的诊断和治疗能力。

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引用次数: 0

Recent updates on novel heterocyclic scaffolds of anticancer potential as emerging tubulin inhibitors 新型杂环支架作为新兴微管蛋白抑制剂抗癌潜力的最新进展

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-24 DOI: 10.1016/j.seminoncol.2025.152374

Sahil Kumar , Urvashi Gupta , Rajesh Kumar Singh

Cancer remains a leading cause of mortality worldwide, accounting for approximately one in six deaths. Among the most prevalent cancer types are prostate, lung, colon, and rectal cancers. Despite significant investments in research, the therapeutic success of modern cancer treatments remains limited compared to other life-threatening diseases. In the pursuit of novel anticancer strategies, microtubules—dynamic cytoskeletal structures essential for cellular processes such as mitosis, intracellular transport, and signaling—have emerged as attractive drug targets. This review provides a comprehensive overview of recent advancements in the design and synthesis of novel heterocyclic scaffolds as tubulin inhibitors, emphasizing their potential as anticancer agents. Heterocyclic compounds exhibit unique therapeutic properties that disrupt microtubule dynamics, inducing cell cycle arrest and apoptosis in rapidly proliferating cancer cells. The article systematically classifies and critically evaluates diverse heterocyclic scaffolds, including both natural products and synthetic derivatives, with a focus on their interactions with the microtubule cytoskeleton at a molecular level. By consolidating current insights into these emerging scaffolds, this review serves as a valuable resource for the development of next-generation anticancer therapeutics targeting tubulin.

癌症仍然是全世界死亡的主要原因，约占死亡人数的六分之一。最常见的癌症类型是前列腺癌、肺癌、结肠癌和直肠癌。尽管在研究方面投入了大量资金，但与其他危及生命的疾病相比，现代癌症治疗的成功仍然有限。在追求新的抗癌策略的过程中，微管作为细胞过程如有丝分裂、细胞内运输和信号传导所必需的动态细胞骨架结构，已经成为有吸引力的药物靶点。本文综述了作为微管蛋白抑制剂的新型杂环支架的设计和合成的最新进展，强调了它们作为抗癌药物的潜力。杂环化合物在快速增殖的癌细胞中表现出独特的治疗特性，破坏微管动力学，诱导细胞周期阻滞和细胞凋亡。本文对各种杂环支架进行了系统的分类和严格的评价，包括天然产物和合成衍生物，重点关注它们在分子水平上与微管细胞骨架的相互作用。通过巩固目前对这些新兴支架的见解，本综述为开发针对微管蛋白的下一代抗癌疗法提供了宝贵的资源。

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引用次数: 0

Breast cancer exosomes: Managing macrophage polarization and immune regulation in the tumor microenvironment 乳腺癌外泌体：在肿瘤微环境中管理巨噬细胞极化和免疫调节

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-20 DOI: 10.1016/j.seminoncol.2025.152365

Suleiman Ibrahim Mohammad , Ehab Yassen Theab , Asokan Vasudevan , Ashok Kumar Bishoyi , Suhas Ballal , Hussein Riyadh Abdul Kareem Al-Hetty , Aman Shankhyan , Anupria A , Rajashree Panigrahi , Hatif Abdulrazaq Yasin

Exosomes are sub-150 nm extracellular vesicles mediating intercellular messaging in breast cancer's complex tumor microenvironment (TME). Produced by both tumor cells and their stroma components, these vesicles excrete various biomolecules, such as microRNAs (miRNAs), proteins, lipids, and even DNA fragments, enabling a functional exchange of information among cells. In breast cancer, different studies indicate a significant role of exosome-mediated signaling in modulating the phenotype of tumor-associated macrophages (TAMs), mainly polarizing them toward an M2-like phenotype, further supporting the potentiality for tumor-promoting functions. This review will detail the diverse roles of breast cancer-derived exosomes and macrophage polarization and elaborate on their recognized pathways by which these vesicles casually alter the macrophage phenotype. In our discussion, we take a broad detour to deeply examine the unique molecular accessories delivered by breast cancer exosomes. In particular, we discuss the miRNAs suppressed by M1-associated gene expression and those endowing M2-related pathways with abilities, and we cover the proteins that activate pathways like the STAT3 and NF-κB pathways in macrophages. This review will also address the relevance of mechanistic issues to clinical manifestation in exosome-mediated macrophage polarization in breast cancer. Finally, targeting exosome-mediated macrophage polarization as a promising strategy to enhance antitumor immunity in conjunction with improving breast cancer outcomes is deliberated.

外泌体是在乳腺癌复杂肿瘤微环境（TME）中介导细胞间信息传递的低于150 nm的细胞外囊泡。这些囊泡由肿瘤细胞及其基质成分产生，分泌各种生物分子，如microrna （miRNAs）、蛋白质、脂质，甚至DNA片段，使细胞间的信息功能交换成为可能。在乳腺癌中，不同的研究表明，外泌体介导的信号传导在调节肿瘤相关巨噬细胞（tam）的表型中发挥着重要作用，主要是将其极化为m2样表型，进一步支持了其促肿瘤功能的可能性。本文将详细介绍乳腺癌源性外泌体和巨噬细胞极化的不同作用，并阐述这些囊泡随意改变巨噬细胞表型的公认途径。在我们的讨论中，我们采取广泛的迂回，深入研究乳腺癌外泌体传递的独特分子附件。特别地，我们讨论了被m1相关基因表达抑制的mirna和那些赋予m2相关通路能力的mirna，并涵盖了巨噬细胞中激活STAT3和NF-κB通路等通路的蛋白质。本综述还将讨论外泌体介导的巨噬细胞极化在乳腺癌中与临床表现的机制问题的相关性。最后，针对外泌体介导的巨噬细胞极化作为一种增强抗肿瘤免疫并改善乳腺癌预后的有希望的策略进行了讨论。

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引用次数: 0