Seminars in oncology最新文献_第7页

The dual effect of interferon-γ in acute myeloid leukemia: A narrative review 干扰素-γ在急性髓系白血病中的双重作用：综述

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-05-05 DOI: 10.1016/j.seminoncol.2025.152347

Abiy Ayele Angelo , Gashaw Adane , Dereje Mengesha Berta , Elias Chane , Negesse Cherie , Mebratu Tamir , Bisrat Birke Teketelew

Acute myeloid leukemia (AML) is a hematological malignancy representing a very rapid, uncontrolled growth of myeloid precursors in the BM and peripheral circulation. Studies on AML have highlighted the crucial role of IFN-γ therapy in immune surveillance, both promotive and inhibitory effects on leukemic cells, and regulation of the tumor microenvironment. However, there is a need for a comprehensive understanding of the dual effects of IFN-γ in AML. Thus, this review aimed to assess the dual effects of IFN-γ in AML. Literature searches were conducted in Pub Med, Google Scholar, and direct Google Search. The data was presented in tables and figures, with findings summarized through a narrative synthesis. Depending on the circumstances and stage of the disease IFN-γ shows two different activities in AML patients. First, IFN-γ enhances NK cells and CD8⁺ T lymphocyte functions, which collectively evoke antileukemic immunity. Another promising effect of IFN-γ includes the differentiation of myeloid cells, thereby possibly reducing the severity of leukemia. However, prolonged exposure to IFN-γ can activate Treg cells and inhibitory immunological checkpoints, which can help leukemia evade immune surveillance and encounter an immunosuppressive environment. Our review highlights IFN-γ's critical role in the complex interplay between the immune system and AML pathogenesis. Its dual role in both inhibiting and promoting leukemic processes has been highlighted. However, future pre-clinical and clinical studies should focus on the specific mechanisms by which IFN-γ impacts AML progression and treatment outcomes, with the goal of achieving curative results for patients.

急性髓性白血病（AML）是一种血液系统恶性肿瘤，表现为骨髓前体在骨髓和外周循环中非常迅速、不受控制的生长。AML的研究强调了IFN-γ治疗在免疫监视中的关键作用，对白血病细胞的促进和抑制作用，以及肿瘤微环境的调节。然而，有必要全面了解IFN-γ在AML中的双重作用。因此，本综述旨在评估IFN-γ在AML中的双重作用。文献检索在Pub Med、b谷歌Scholar和直接谷歌Search中进行。数据以表格和图表的形式呈现，并通过叙述综合的方式总结了调查结果。根据情况和疾病的分期，IFN-γ在AML患者中表现出两种不同的活性。首先，IFN-γ增强NK细胞和CD8+ T淋巴细胞功能，共同唤起抗白血病免疫。IFN-γ的另一个有希望的作用包括骨髓细胞的分化，从而可能降低白血病的严重程度。然而，长期暴露于IFN-γ可以激活Treg细胞和抑制免疫检查点，这可以帮助白血病逃避免疫监视并遇到免疫抑制环境。我们的综述强调了IFN-γ在免疫系统和AML发病机制之间复杂的相互作用中的关键作用。它在抑制和促进白血病过程中的双重作用已被强调。然而，未来的临床前和临床研究应关注IFN-γ影响AML进展和治疗结果的具体机制，以实现患者的治愈效果。

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Divergent functions of TLRs in gastrointestinal (GI) cancer: Overview of their diagnostic, prognostic and therapeutic value tlr在胃肠道（GI）肿瘤中的不同功能：其诊断、预后和治疗价值综述

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-05-09 DOI: 10.1016/j.seminoncol.2025.152344

Chou-Yi Hsu , Saade Abdalkareem Jasim , Khetam Habeeb Rasool , Malathi H , Jaswinder Kaur , Majid S. Jabir , Sharif Alhajlah , Abhinav Kumar , Sabrean F. Jawad , Beneen Husseen

The relationship between the innate immune signal and the start of the adaptive immune response is the central idea of this theory. By controlling the inflammatory and tissue-repair reactions to damage, the Toll-like receptors (TLRs), as a family of PRRs, have attracted increasing attention for its function in protecting the host against infection and preserving tissue homeostasis. Microbial infection, damage, inflammation, and tissue healing have all been linked to the development of malignancies, especially gastrointestinal (GI) cancers. Recently, increased studies on TLR recognition and binding, as well as their ligands, have significantly advanced our knowledge of the various TLR signaling pathways and offered therapy options for GI malignancies. Upon activation by pathogen-associated or damage-associated molecular patterns (DAMPs and PAMPs), TLRs trigger key pathways like NF-κB, MAPK, and IRF. NF-κB activation promotes inflammation, cell survival, and proliferation, often contributing to tumor growth, metastasis, and therapy resistance. MAPK pathways similarly drive uncontrolled cell growth and invasion, while IRF pathways modulate interferon production, yielding both anti-tumor and protumor effects. The resulting chronic inflammatory environment within tumors can foster progression, yet TLR activation can also stimulate beneficial anti-tumor immune responses. However, the functions of TLR expression in GI cancers and their diagnostic and prognostic along with therapeutic value have not yet entirely been elucidated. Understanding how TLR activation contributes to anti-cancer immunity against GI malignancies may hasten immunotherapy developments and increase patient survival.

先天免疫信号与适应性免疫反应开始之间的关系是该理论的中心思想。toll样受体（Toll-like receptors, TLRs）作为PRRs家族中的一员，通过控制机体对损伤的炎症和组织修复反应，其在保护宿主免受感染和维持组织稳态方面的功能越来越受到人们的关注。微生物感染、损伤、炎症和组织愈合都与恶性肿瘤的发展有关，尤其是胃肠道（GI）癌症。最近，对TLR识别和结合及其配体的研究增加，大大提高了我们对各种TLR信号通路的认识，并为胃肠道恶性肿瘤的治疗提供了选择。在被病原体相关或损伤相关分子模式（DAMPs和PAMPs）激活后，TLRs触发NF-κB、MAPK和IRF等关键通路。NF-κB活化促进炎症、细胞存活和增殖，通常有助于肿瘤生长、转移和治疗抵抗。MAPK通路同样驱动不受控制的细胞生长和侵袭，而IRF通路调节干扰素的产生，产生抗肿瘤和肿瘤的作用。由此产生的肿瘤内的慢性炎症环境可以促进进展，但TLR激活也可以刺激有益的抗肿瘤免疫反应。然而，TLR表达在胃肠道肿瘤中的功能及其诊断、预后和治疗价值尚未完全阐明。了解TLR激活如何促进对胃肠道恶性肿瘤的抗癌免疫，可能会加速免疫治疗的发展，提高患者的生存率。

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Advances and challenges in cancer immunotherapy: Strategies for personalized treatment 癌症免疫治疗的进展与挑战：个性化治疗策略

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-04-29 DOI: 10.1016/j.seminoncol.2025.152345

Mahir Azmal, Md. Munna Miah, Fatema Sultana Prima, Jibon Kumar Paul, ANM Shah Newaz Been Haque, Ajit Ghosh

Cancer immunotherapy has transformed oncology by harnessing the immune system to specifically target cancer cells, offering reduced systemic toxicity compared to traditional therapies. This review highlights key strategies, including adoptive cell transfer (ACT), immune checkpoint inhibitors, oncolytic viral (OV) therapy, monoclonal antibodies (mAbs), and mRNA-based vaccines. ACT reinfuses enhanced immune cells like tumor-infiltrating lymphocytes (TILs) to combat refractory cancers, while checkpoint inhibitors (eg, PD-1 and CTLA-4 blockers) restore T-cell activity. OV therapy uses engineered viruses (eg, T-VEC) to selectively lyse cancer cells, and advanced mAbs improve targeting precision. mRNA vaccines introduce tumor-specific antigens to trigger robust immune responses. Despite significant progress, challenges like immune-related side effects, high costs, and immunosuppressive tumor microenvironments persist. This review underscores the need for combination strategies and precision medicine to overcome these barriers and maximize the potential of immunotherapy in personalized cancer treatment.

与传统疗法相比，癌症免疫疗法通过利用免疫系统特异性靶向癌细胞，降低了全身毒性，从而改变了肿瘤学。这篇综述强调了关键策略，包括过继细胞转移（ACT）、免疫检查点抑制剂、溶瘤病毒（OV）治疗、单克隆抗体（mab）和基于mrna的疫苗。ACT重新注入增强的免疫细胞，如肿瘤浸润淋巴细胞（til），以对抗难治性癌症，而检查点抑制剂（如PD-1和CTLA-4阻滞剂）恢复t细胞活性。OV疗法使用工程病毒（如T-VEC）选择性地裂解癌细胞，先进的单克隆抗体提高靶向精度。mRNA疫苗引入肿瘤特异性抗原以触发强大的免疫反应。尽管取得了重大进展，但免疫相关副作用、高成本和免疫抑制肿瘤微环境等挑战仍然存在。这篇综述强调需要联合策略和精准医学来克服这些障碍，并最大限度地发挥免疫治疗在个性化癌症治疗中的潜力。

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Epidemiology and prevention of gastric cancer: A comprehensive review 胃癌的流行病学和预防：综述

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-04-29 DOI: 10.1016/j.seminoncol.2025.152341

Smruti Priyambada Pradhan , Ayushman Gadnayak , Sukanta Kumar Pradhan , Venkatarao Epari

Gastric cancer is the third most deadly cancer worldwide. Helicobacter pylori (H. pylori) infection and specific diets are key risk factors for this illness, which is more frequent in various nations. Nearly half of the world's population, 4.4 billion, had H. pylori in 2015. East has a higher incidence rate than West. GC may spread to the liver, lungs, and bones. The majority of cases are adenocarcinomas (90%). In 2022, stomach cancer caused 968,784 new cases and 660,175 deaths worldwide. GC accounts for 7% of cancer diagnoses and 9% of deaths. The high death rate of gastric cancer highlights the need for preventative methods to improve prognosis. Early identification via biomarker screening, especially in high-risk groups, may improve outcomes and treatments.

胃癌是世界上第三大致命癌症。幽门螺杆菌（h.p ylori）感染和特定的饮食是这种疾病的关键危险因素，这种疾病在各个国家都很常见。2015年，全球近一半的人口（44亿）感染了幽门螺旋杆菌。东部的发病率比西部高。胃癌可扩散到肝、肺和骨骼。大多数病例为腺癌（90%）。2022年，胃癌在全球造成968,784例新病例和660,175例死亡。胃癌占癌症诊断的7%，占死亡的9%。胃癌的高死亡率突出表明需要采取预防措施来改善预后。通过生物标志物筛选的早期识别，特别是在高危人群中，可能会改善结果和治疗。

引用次数: 0

Mechanistic role of FTO in cancer pathogenesis, immune evasion, chemotherapy resistance, and immunotherapy response FTO在癌症发病、免疫逃避、化疗耐药和免疫治疗反应中的机制作用

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 10.1016/j.seminoncol.2025.152368

Sarah Qutayba Badraldin , Karar H. Alfarttoosi , Hayder Naji Sameer , Ashok Kumar Bishoyi , Subbulakshmi Ganesan , Aman Shankhyan , Subhashree Ray , Deepak Nathiya , Ahmed Yaseen , Zainab H. Athab , Mohaned Adil

Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) RNA demethylase, plays a key role in cancer biology by regulating mRNA modifications. Its deregulation affects tumor cell proliferation, metastasis, immune evasion, and therapeutic resistance. By removing m6A methylation marks, FTO can alter the stability and translation of key oncogenes and tumor suppressor genes. These modifications directly influence essential cellular pathways involved in cancer progression, such as the phosphatidylinositol 3-kinases/ protein kinase B (PI3K/AKT), Wnt/β-catenin, and mammalian target of rapamycin (mTOR) signaling pathways. This review explores the mechanistic roles of FTO in cancer pathogenesis, focusing on its dual impact on immune regulation and chemotherapy response. In terms of immunity, FTO has been shown to promote immune evasion by modulating the expression of immune checkpoints and influencing the tumor microenvironment. Additionally, FTO’s influence on autophagy, glycolysis, and apoptosis resistance further complicates the effectiveness of chemotherapy treatments. By discussing the molecular details of how FTO regulates these processes, we provide insights into how FTO could serve as a promising therapeutic target to overcome cancer-related challenges, including immune resistance and chemotherapy failure. Finally, we evaluate current and emerging strategies for targeting FTO in cancer therapy, highlighting its potential to enhance immunotherapy and chemotherapy outcomes.

脂肪质量和肥胖相关蛋白（FTO）是一种n6 -甲基腺苷（m6A） RNA去甲基化酶，通过调节mRNA修饰在癌症生物学中发挥关键作用。它的解除影响肿瘤细胞的增殖、转移、免疫逃避和治疗抵抗。通过去除m6A甲基化标记，FTO可以改变关键癌基因和肿瘤抑制基因的稳定性和翻译。这些修饰直接影响了参与癌症进展的基本细胞通路，如磷脂酰肌醇3-激酶/蛋白激酶B （PI3K/AKT）、Wnt/β-catenin和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。本文综述了FTO在肿瘤发病机制中的作用，重点探讨了FTO在免疫调节和化疗反应中的双重作用。在免疫方面，FTO已被证明通过调节免疫检查点的表达和影响肿瘤微环境来促进免疫逃避。此外，FTO对自噬、糖酵解和细胞凋亡抵抗的影响进一步复杂化了化疗的有效性。通过讨论FTO如何调节这些过程的分子细节，我们提供了FTO如何作为一个有希望的治疗靶点来克服癌症相关的挑战，包括免疫抵抗和化疗失败的见解。最后，我们评估了当前和新兴的针对FTO的癌症治疗策略，强调了其增强免疫治疗和化疗结果的潜力。

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引用次数: 0

The Crucial Nexus: Unveiling the Role of Collagen in Cancer Progression 关键的联系：揭示胶原蛋白在癌症进展中的作用

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 10.1016/j.seminoncol.2025.152346

Hazel Reeva , Godson Mahesh , Uma Manjunath, Nagarajan Selvamurugan, Durairaj MohanKumar

The complex interplay between collagen and cancer cells within the tumor microenvironment (TME) highlights the pivotal role of collagens in cancer progression, prognosis and therapy resistance. As a critical structural protein of the extracellular matrix (ECM), collagen not only maintains tissue architecture but also regulates key physiological functions through complex biosynthetic pathways. Deregulation in collagen biosynthesis, characterized by abnormal transcription, post-translational modifications, and deposition, contributes to ECM remodeling and tumor progression. This review explores the involvement of diverse collagen family members in cancer progression across multiple cancer types. Several collagen isoforms have emerged as key players in cancer progression, influencing tumor behavior and act as potential biomarkers for prognosis. Furthermore, circulating collagen fragments in blood present promising avenues for non-invasive cancer diagnosis and disease monitoring. Tumor collagen remodeling alters ECM architecture, impacting tumor-stromal interactions and fostering a microenvironment conducive to favour invasion and metastasis. Mechanistic insights reveal that collagen-induced signalling pathways are the major drivers of stemness, drug resistance, EMT, metastasis, angiogenesis and immune evasion, which collectively shape tumor cell behavior and immune infiltration dynamics. Further, targeting tumor collagen appear to be a viable and robust strategy to treat aggressive desmoplastic and metastatic cancers.

肿瘤微环境（tumor microenvironment， TME）中胶原蛋白与癌细胞之间复杂的相互作用凸显了胶原蛋白在癌症进展、预后和治疗耐药中的关键作用。胶原蛋白作为细胞外基质（extracellular matrix， ECM）的关键结构蛋白，不仅维持组织结构，还通过复杂的生物合成途径调节关键的生理功能。胶原生物合成的失调，以异常转录、翻译后修饰和沉积为特征，有助于ECM重塑和肿瘤进展。这篇综述探讨了多种胶原蛋白家族成员在多种癌症类型的癌症进展中的参与。几种胶原异构体已经成为癌症进展的关键参与者，影响肿瘤行为并作为预后的潜在生物标志物。此外，血液中循环的胶原蛋白片段为非侵入性癌症诊断和疾病监测提供了有希望的途径。肿瘤胶原重塑改变ECM结构，影响肿瘤与基质的相互作用，培养有利于侵袭和转移的微环境。机制揭示了胶原诱导的信号通路是干细胞、耐药、EMT、转移、血管生成和免疫逃避的主要驱动因素，它们共同塑造了肿瘤细胞的行为和免疫浸润动力学。此外，靶向肿瘤胶原蛋白似乎是治疗侵袭性结缔组织增生和转移性癌症的一种可行和强大的策略。

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引用次数: 0

Integrated analysis of scRNA-seq and bulk RNA-seq data identifies BHLHE40 as a key gene in pancreatic cancer progression and gemcitabine resistance 综合分析scRNA-seq和大量RNA-seq数据，确定BHLHE40是胰腺癌进展和吉西他滨耐药的关键基因

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-04-01 Epub Date: 2025-04-17 DOI: 10.1016/j.seminoncol.2025.152338

Yang Wu , Chun Zhang , Jiacheng Huang , Qun Chen , Yufeng Zhang , Fengyuan Liu , Dong Xu , Kuirong Jiang , Run Shi , Mengxing Chen , Hao Yuan

Objective

Pancreatic cancer is characterized by its high mortality rate and short survival periods, and novel therapeutic targets and tailor personalized strategies are urgently needed. In this study, we aim to investigate the molecular mechanisms underlying pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance, with a focus on identifying novel therapeutic targets.

Methods

Multiomics approaches were integrated to identify novel actionable targets for PDAC. Public datasets such as TCGA and GEO were utilized to investigate the relationship between gene expression and clinical outcomes. Functional enrichment, cell-cell communication, and metabolic pathway analyses were performed to reveal PDAC heterogeneity and therapeutic resistance mechanisms.

Results

BHLHE40 was identified as a hub gene linked to high-CNV PDAC cells, Gemcitabine resistance, and poor prognosis in PDAC. High BHLHE40 expression is significantly correlated with immunosuppressive tumor microenvironment (TME) features such as reduced CD8+ T infiltration, TCR richness, and lower tumor mutational burden (TMB). ChIP-seq data analysis confirmed BHLHE40 could directly bind to the SAT1 promoter, establishing a transcriptional axis promoting chemoresistance. Single-cell RNA-seq analysis further revealed that the BHLHE40+/SAT1+ subpopulation cells are resistant to Gemcitabine in PDAC.

Conclusions

BHLHE40 is significantly correlated with PDAC malignancy and chemoresistance via SAT1 regulation and immune evasion. Targeting BHLHE40 may sensitize PDACs to Gemcitabine and facilitate personalized treatment for BHLHE40+ PDAC patients.

目的胰腺癌具有死亡率高、生存期短的特点，迫切需要新的治疗靶点和个性化治疗策略。在这项研究中，我们的目的是研究胰腺导管腺癌（PDAC）进展和化疗耐药的分子机制，重点是寻找新的治疗靶点。方法采用多组学方法鉴定PDAC新的可操作靶点。利用TCGA和GEO等公共数据集来研究基因表达与临床结果的关系。功能富集、细胞间通讯和代谢途径分析揭示了PDAC的异质性和治疗耐药机制。结果bhlhe40被鉴定为高cnv PDAC细胞、吉西他滨耐药和PDAC不良预后相关的枢纽基因。BHLHE40高表达与免疫抑制肿瘤微环境（TME）特征显著相关，如CD8+ T浸润减少、TCR丰富度降低、肿瘤突变负担（TMB）降低。ChIP-seq数据分析证实BHLHE40可以直接结合SAT1启动子，建立一个促进化学耐药的转录轴。单细胞RNA-seq分析进一步显示BHLHE40+/SAT1+亚群细胞在PDAC中对吉西他滨耐药。结论shbhlhe40通过SAT1调控和免疫逃逸与PDAC恶性肿瘤及化疗耐药相关。靶向BHLHE40可能使PDAC对吉西他滨敏感，促进BHLHE40+ PDAC患者的个性化治疗。

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引用次数: 0

Plant polyphenols in gastric cancer: Nature's healing touch 胃癌中的植物多酚：大自然的治愈之触

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-04-01 Epub Date: 2025-03-11 DOI: 10.1053/j.seminoncol.2025.01.002

Chengu Niu , Jing Zhang , Patrick I. Okolo III , Ebubekir Daglilar

Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.

在全球范围内，胃癌在最常见的癌症中排名第五，是恶性肿瘤相关死亡的第三大常见原因。虽然手术是胃癌的主要治疗选择，但辅助化疗可以提高手术后患者的生存率。众所周知，植物多酚具有许多有益健康的作用，包括抗癌特性。大量研究表明，植物多酚类物质在体外和体内对胃癌具有潜在的抗癌作用，但人体研究很少。然而，这一主题尚未得到审查。目前的研究表明，植物多酚对胃癌的潜在抗癌作用初步归因于其抗增殖、抗转移、抗血管生成以及调节细胞凋亡、自噬和细胞内活性氧的作用。此外，常规疗法联合植物多酚使胃癌细胞对常规疗法更敏感。我们还讨论了将植物多酚为基础的治疗转化为临床应用的挑战和机遇。本综述提供的内容对从事植物医学研究的药理学家、民族植物学家和肿瘤学家很有兴趣。

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引用次数: 0

High tumor mutation burden mitigates the negative impact of chemotherapy history on immune checkpoint blockade therapy 高肿瘤突变负荷减轻了化疗史对免疫检查点阻断治疗的负面影响

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-04-01 Epub Date: 2025-03-12 DOI: 10.1053/j.seminoncol.2025.01.003

Ming Zheng MD, PhD

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC. ICI therapy has revolutionized treatment, but prior chemotherapy may diminish ICI treatment efficacy. Tumor mutation burden (TMB) has emerged as a crucial predictor of ICI response, yet its interaction with chemotherapy history in ICI therapy is not fully understood. In this study, I investigate the impact of chemotherapy history on ICI treatment outcomes, focusing on TMB as a potential mitigating factor. Analyzing data from 512 patients with advanced NSCLC treated with PD-1/PD-L1 or CTLA-4 inhibitors, this sudy found that prior chemotherapy significantly reduced objective response rates (ORR) to ICI therapy, particularly in patients with low TMB (<15 mut/Mb). However, in patients with high TMB (≥15 mut/Mb), the negative impact of chemotherapy history on ICI treatment efficacy is minimal, suggesting that high TMB mitigates chemotherapy-induced resistance to ICI therapy. Furthermore, while chemotherapy history is associated with worse overall survival (OS) and progression-free survival (PFS) following ICI therapy in low-TMB patients, no such association is observed in high-TMB patients. These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.

肺癌仍然是全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）占大多数病例。免疫检查点抑制剂（ICI）治疗，特别是PD-1抑制剂如nivolumab，已成为晚期NSCLC的关键治疗选择。ICI治疗是一种革命性的治疗方法，但先前的化疗可能会降低ICI治疗的效果。肿瘤突变负荷（Tumor mutation burden， TMB）已成为ICI反应的重要预测指标，但其与ICI治疗中化疗史的相互作用尚不完全清楚。在本研究中，我研究了化疗史对ICI治疗结果的影响，重点关注TMB作为潜在的缓解因素。本研究分析了512例接受PD-1/PD-L1或CTLA-4抑制剂治疗的晚期非小细胞肺癌患者的数据，发现既往化疗显著降低了对ICI治疗的客观缓解率（ORR），特别是低TMB （<15 mut/Mb）患者。然而，在高TMB（≥15 mut/Mb）的患者中，化疗史对ICI治疗疗效的负面影响很小，这表明高TMB减轻了化疗诱导的ICI治疗耐药。此外，虽然化疗史与低tmb患者ICI治疗后的总生存期（OS）和无进展生存期（PFS）较差相关，但在高tmb患者中没有观察到这种关联。这些发现强调了TMB作为一种预测性生物标志物的重要性，强调了优化治疗序列和个性化治疗策略的必要性，以克服化疗诱导的免疫抵抗并最大化ICI治疗效果。这些结果表明，ICI治疗作为一线治疗可能更有益，特别是对于低TMB患者。

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引用次数: 0

The interest of therapeutic and pharmacological drug monitoring of methotrexate: A systematic review 甲氨蝶呤治疗和药物监测的意义：系统综述

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-04-01 Epub Date: 2025-04-16 DOI: 10.1016/j.seminoncol.2025.152342

Wissal Chellal , Youssra Metarfi , Zineb Ben khadda , Hasnae Hoummani , Rhizlane Berrady , Sanae Achour

Methotrexate (MTX) is largely prescribed for cancers, particularly hematological malignancies. To reduce its toxicity, therapeutic drug monitoring (TDM) is highly recommended. This review aimed to assess knowledge on methotrexate monitoring and compare strategies for managing its toxicities. We searched several databases for articles that met the selection criteria. All articles were screened and data on analytical methods, results, and toxicities were extracted. Thirty articles were included in this review, consisting mainly of single-center studies. MTX monitoring studies have been conducted in various countries. Patient demographics covered children and adults, with one study focusing on elderly patients. MTX doses varied primarily between high-dose regimens. Sample collection times were varied. Various techniques were used to quantify MTX levels. This review highlights the diversity of study designs, patient populations, dosing regimens, and analytical techniques, emphasizing the need for standardized protocols and further research to optimize MTX treatment, ensuring both efficacy and safety.

甲氨蝶呤（MTX）主要用于治疗癌症，特别是血液系统恶性肿瘤。为了降低其毒性，强烈建议进行治疗性药物监测（TDM）。本综述旨在评估甲氨蝶呤监测方面的知识，并比较管理其毒性的策略。我们在几个数据库中搜索了符合选择标准的文章。对所有文章进行筛选，提取分析方法、结果和毒性的数据。本综述纳入了30篇文章，主要为单中心研究。在许多国家进行了MTX监测研究。患者人口统计包括儿童和成人，其中一项研究侧重于老年患者。甲氨蝶呤的剂量主要在高剂量方案之间变化。样品采集时间各不相同。各种技术用于量化MTX水平。这篇综述强调了研究设计、患者群体、给药方案和分析技术的多样性，强调需要标准化的方案和进一步的研究来优化MTX治疗，确保疗效和安全性。

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引用次数: 0