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Prospects of nano-theranostic approaches against breast and cervical cancer 纳米治疗乳腺癌和宫颈癌的前景。

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.2024.189227

Tasnim Ria , Rubi Roy , Uma Sankar Mandal , Ugir Hossain Sk

The bottleneck on therapeutics and diagnostics is removed by an alternate approach known as theranostics which combines both therapeutics and diagnostics within a single platform. Due to this “all in one” nature of theranostics, it is now extensively applied in the medicinal field mainly in cancer treatment over the conventional therapy. Recently, FDA approval of lutetium 177 (177Lu) DOTATATE and 177Lu–PSMA-based radionuclide theranostics are clinically used and very few theranostics specific to breast cancer are in clinical trials. In this review, we are willing to draw special attention to the application of theranostics in the most relevant cancers in women, the breast and the cervical as these cancers affect women harshly but talked very silently due to the social restrictions and discriminations mainly in rural areas of developing and under developing countries. This approach not only combines therapeutics and diagnostics but targeting moieties can also be accommodated for the precise medication. Herein, our main objective is to enlighten the broader aspects of different kinds of theranostic devices based on radioisotopes, nanoparticles, graphene quantum dots, dendrimers and their fruitful application against breast and cervical cancer. The development of synthetic nano-theranostics was reported by accommodating therapeutic drugs, imaging probes and targeting ligands through conjugation or encapsulation. The imaging modalities like optical fluorescence, photosensitizers and radiotracers are used to get the diagnostic images through NIR, PET, MRI and CT/SPECT to detect the progress of cancer non-invasively and also at the same time targeting ligands such as antibodies, proteins and peptides in attachment with the theranostics enhances the therapeutic efficacy in addition to the clarity in diagnostics. The applications of theranostics from the last decade with their present scenario in clinics and future perspectives, as well as the pitfalls with the hurdles that still leave questions to rethink from the root are also been discussed in this review.

治疗学和诊断学的瓶颈被另一种称为治疗学的方法所消除，该方法将治疗学和诊断学结合在一个平台内。由于治疗学的这种“一体”的性质，它现在被广泛应用于医学领域，主要是癌症治疗，而不是传统治疗。最近，FDA批准了177 (177Lu) DOTATATE和177Lu- psma为基础的放射性核素治疗药物在临床使用，并且很少有针对乳腺癌的治疗药物处于临床试验中。在这篇综述中，我们愿意特别关注治疗学在与妇女最相关的癌症，乳腺癌和宫颈癌中的应用，因为这些癌症对妇女的影响很大，但由于社会的限制和歧视，主要在发展中国家和欠发展中国家的农村地区，人们很少谈论这些癌症。这种方法不仅结合了治疗和诊断，而且靶向部分也可以适应精确的药物治疗。在此，我们的主要目标是启发基于放射性同位素、纳米颗粒、石墨烯量子点、树突状分子的不同类型的治疗装置及其在乳腺癌和宫颈癌中的有效应用的更广泛方面。本文报道了通过缀合或包封的方法来容纳治疗药物、成像探针和靶向配体的合成纳米治疗学的发展。利用光学荧光、光敏剂、放射性示踪剂等成像方式，通过NIR、PET、MRI、CT/SPECT等获得诊断图像，无创伤地检测癌症的进展，同时靶向附着的配体如抗体、蛋白质、多肽等治疗药物，提高了治疗效果，诊断更加清晰。本综述还讨论了过去十年来治疗学在临床和未来前景中的应用，以及仍然需要从根本上重新思考的问题的陷阱和障碍。

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引用次数: 0

Multifaceted roles of neutrophils in tumor microenvironment 中性粒细胞在肿瘤微环境中的多方面作用

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.2024.189231

Xueyin Pan , Qiang Wang , Beicheng Sun

Neutrophils, the most abundant leukocyte population in circulation, play a crucial role in detecting and responding to foreign cells, such as pathogens and tumor cells. However, the impact of neutrophils on cancer pathogenesis has been overlooked because of their short lifespan, terminal differentiation, and limited transcriptional activity. Within the tumor microenvironment (TME), neutrophils can be influenced by tumor cells or other stromal cells to acquire either protumor or antitumor properties via the cytokine environment. Despite progress in neutrophil-related research, a comprehensive understanding of tissue-specific neutrophil diversity and adaptability in the TME is still lacking, which poses a significant obstacle to the development of neutrophil-based cancer therapies. This review evaluated the current studies on the dual roles of neutrophils in cancer progression, emphasizing their importance in predicting clinical outcomes, and explored various approaches for targeting neutrophils in cancer treatment, including their potential synergy with cancer immunotherapy.

中性粒细胞是循环中最丰富的白细胞群，在检测和应答外来细胞（如病原体和肿瘤细胞）方面起着至关重要的作用。然而，由于中性粒细胞寿命短、终末分化和转录活性有限，它们在癌症发病中的作用一直被忽视。在肿瘤微环境（TME）中，中性粒细胞可以受到肿瘤细胞或其他基质细胞的影响，通过细胞因子环境获得肿瘤或抗肿瘤特性。尽管中性粒细胞相关研究取得了进展，但对TME中组织特异性中性粒细胞多样性和适应性的全面了解仍然缺乏，这对基于中性粒细胞的癌症治疗的发展构成了重大障碍。本文综述了目前关于中性粒细胞在癌症进展中的双重作用的研究，强调了它们在预测临床结果方面的重要性，并探讨了针对中性粒细胞在癌症治疗中的各种方法，包括它们与癌症免疫治疗的潜在协同作用。

引用次数: 0

Methyltransferases in cancer drug resistance: Unlocking the potential of targeting SMYD3 to sensitize cancer cells 癌症耐药性中的甲基转移酶：发掘靶向 SMYD3 使癌细胞敏感的潜力。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.bbcan.2024.189203

Paola Sanese , Candida Fasano , Martina Lepore Signorile , Katia De Marco , Giovanna Forte , Vittoria Disciglio , Valentina Grossi , Cristiano Simone

Drug resistance is a significant challenge in oncology and is driven by various mechanisms, among which a crucial role is played by enhanced DNA repair. Thus, targeting DNA damage response (DDR) factors with specific inhibitors is emerging as a promising therapeutic strategy. An important process involved in the modulation of DNA repair pathways, and hence in drug resistance, is post-translational modification (PTM). PTMs such as methylation affect protein function and are critical in cancer biology. Methylation is catalyzed by specific enzymes called protein methyltransferases. In recent years, the SET domain-containing N-lysine methyltransferase SMYD3 has emerged as a significant oncogenic driver. It is overexpressed in several tumor types and plays a signal-dependent role in promoting gastrointestinal cancer formation and development. Recent evidence indicates that SMYD3 is involved in the maintenance of cancer genome integrity and contributes to drug resistance in response to genotoxic stress by regulating DDR mechanisms. Several potential SMYD3 interactors implicated in DNA repair, especially in the homologous recombination and non-homologous end-joining pathways, have been identified by in silico analyses and confirmed by experimental validation, showing that SMYD3 promotes DDR protein interactions and enzymatic activity, thereby sustaining cancer cell survival. Targeting SMYD3, in combination with standard or targeted therapy, shows promise in overcoming drug resistance in colorectal, gastric, pancreatic, breast, endometrial, and lung cancer models, supporting the integration of SMYD3 inhibition into cancer treatment regimens. In this review, we describe the role played by SMYD3 in drug resistance and analyze its potential as a molecular target to sensitize cancer cells to treatment.

耐药性是肿瘤学面临的一项重大挑战，其驱动机制多种多样，其中 DNA 修复能力的增强发挥了至关重要的作用。因此，以 DNA 损伤应答（DDR）因子为靶点的特异性抑制剂正成为一种前景广阔的治疗策略。DNA 修复途径的一个重要调节过程是翻译后修饰 (PTM)，这也是导致耐药性的一个重要原因。甲基化等 PTM 会影响蛋白质的功能，在癌症生物学中至关重要。甲基化由称为蛋白质甲基转移酶的特定酶催化。近年来，含 SET 结构域的 N-赖氨酸甲基转移酶 SMYD3 已成为一种重要的致癌驱动因子。它在几种肿瘤类型中过度表达，并在促进胃肠癌的形成和发展中发挥着信号依赖性作用。最近的证据表明，SMYD3 参与了癌症基因组完整性的维护，并通过调节 DDR 机制在应对基因毒性压力时产生抗药性。一些潜在的 SMYD3 与 DNA 修复（尤其是同源重组和非同源末端连接途径）有关的相互作用因子已通过硅学分析确定，并通过实验验证得到证实，表明 SMYD3 促进了 DDR 蛋白相互作用和酶活性，从而维持了癌细胞的存活。在结直肠癌、胃癌、胰腺癌、乳腺癌、子宫内膜癌和肺癌模型中，靶向 SMYD3 与标准疗法或靶向疗法相结合，有望克服耐药性，支持将 SMYD3 抑制纳入癌症治疗方案。在这篇综述中，我们描述了 SMYD3 在耐药性中扮演的角色，并分析了其作为分子靶点使癌细胞对治疗敏感的潜力。

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引用次数: 0

The role of ferroptosis resistance in lymph-associated tumour metastasis 铁蛋白抗性在淋巴相关肿瘤转移中的作用。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.bbcan.2024.189200

Xiaoyu Li , Meng Tian , Liuchunyang Yu , JinXiu Qian , Jue Yang , Xiangpeng Wang , Cheng Lu , Cheng Xiao , Yuanyan Liu

Tumour metastasis is a crucial factor in determining clinically challenging tumours. In this respect, the lymphatic system may act as potential entry portals for tumour metastasis, whilst, clinical detection of tumour-infiltrated lymph nodes also indicates poorer prognosis and higher metastatic risk. Whether tumour cells gain ferroptosis resistance in lymph that make them exhibit a stronger propensity for lymphatic dissemination compared to hematogenous spread might be a breakthrough for elucidating lymph-associated tumour metastasis. This review discusses how the lymphatic system endows tumour cells with ferroptosis resistance character, which makes them more propensity for lymph node pre-metastasis and distant metastasis through lymphatic circulation. Comprehensively considering the distinct structure and property of lymph and the unique metabolic characteristics of tumours, all of the lymphatic vessels, intestinal lymph and lymph nodes collectively manipulate an intricate interaction with the hematogenous system and afford substances exchange with tumour cells and extracellular vesicles, upon which make a ferroptosis resistant microenvironment for subsequent metastasis in distant organs and lymph nodes.

肿瘤转移是决定肿瘤是否具有临床挑战性的关键因素。在这方面，淋巴系统可能是肿瘤转移的潜在入口，而临床发现肿瘤浸润淋巴结也表明预后较差，转移风险较高。肿瘤细胞是否会在淋巴中获得抗铁锈色素沉着的能力，从而表现出比血行播散更强的淋巴播散倾向，这可能是阐明淋巴相关肿瘤转移的一个突破口。这篇综述探讨了淋巴系统如何赋予肿瘤细胞以抗铁蛋白性，使其更倾向于淋巴结转移前和通过淋巴循环进行远处转移。综合考虑淋巴的独特结构和性质以及肿瘤的独特代谢特征，所有淋巴管、肠道淋巴和淋巴结共同操纵着与血流系统的复杂互动，并与肿瘤细胞和细胞外囊泡进行物质交换，从而为随后在远处器官和淋巴结的转移创造了抗铁蛋白沉积的微环境。

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引用次数: 0

Dual roles of human endogenous retroviruses in cancer progression and antitumor immune response 人类内源性逆转录病毒在癌症进展和抗肿瘤免疫反应中的双重作用。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.bbcan.2024.189201

Yang Yang, Surong Dong, Benshuai You, Chenglin Zhou

Human endogenous retroviruses (HERVs) are a class of transposable elements formed by the integration of ancient retroviruses into the germline genome. They are inherited in a Mendelian manner and approximately constitute 8 % of the human genome. HERVs were considered as “junk DNA” for decades, but increasing evidence suggests that they play significant roles in pathological inflammation, neural differentiation, and oncogenesis. Specifically, HERVs expression has been implicated in several oncogenic processes and the formation of the tumor microenvironment. Indeed, the dual roles of HERVs in cancer, serving as both promoters of oncogenesis and forerunners of the innate antitumor immune response, remain a subject of debate. In this review, we will discuss how HERVs participate in cancer progression and how they are regulated. Our aim is to provide a comprehensive understanding of the fundamental properties and potential function of HERVs in propagating oncogenesis and activating the antitumor immune response. We hope that updated knowledge will reshape our understanding of the critical roles played by HERVs in human evolution and cancer progression.

人类内源性逆转录病毒（HERVs）是一类转座元件，由古老的逆转录病毒整合到种系基因组中形成。它们以孟德尔方式遗传，约占人类基因组的 8%。几十年来，HERVs 一直被认为是 "垃圾 DNA"，但越来越多的证据表明，它们在病理炎症、神经分化和肿瘤发生中发挥着重要作用。具体来说，HERVs 的表达与多种致癌过程和肿瘤微环境的形成有关。事实上，HERVs 在癌症中的双重作用--既是肿瘤发生的促进因子，又是先天抗肿瘤免疫反应的先驱--仍是一个争论的话题。在本综述中，我们将讨论 HERVs 如何参与癌症进展以及如何对其进行调控。我们的目的是全面了解 HERVs 在传播肿瘤发生和激活抗肿瘤免疫反应方面的基本特性和潜在功能。我们希望最新的知识能够重塑我们对 HERVs 在人类进化和癌症进展中所扮演的关键角色的理解。

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引用次数: 0

CD8+ T-cell exhaustion: Impediment to triple-negative breast cancer (TNBC) immunotherapy CD8+ T 细胞衰竭：三阴性乳腺癌 (TNBC) 免疫疗法的障碍。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-15 DOI: 10.1016/j.bbcan.2024.189193

Dandan Feng , Dongqing Pu , Jinlu Ren , Ming Liu , Zhen Zhang , Zhiyong Liu , Jingwei Li

CD8⁺ T-cell exhaustion has been identified as a significant contributor to immunosuppression and immune escape in triple-negative breast cancer (TNBC). Dysfunction due to cell exhaustion is characterized by reduced effector capacity and sustained expression of inhibitory receptors (IRs). The factors contributing to CD8⁺ T-cell exhaustion are multifaceted, encompassing external influences such as the upregulation of IRs, reduction of effector cytokines, and internal changes within the immune cell, including transcriptomic alterations, epigenetic landscape remodeling, and metabolomic shifts. The impact of the altered TNBC tumor microenvironment (TME) on Tex is also a critical consideration. The production of exhausted CD8⁺ T-cells (CD8⁺ Tex) is positively correlated with poor prognosis and reduced response rates to immunotherapy in TNBC patients, underscoring the urgent need for the development of novel TNBC immunotherapeutic strategies that target the mechanisms of CD8⁺ T-cell exhaustion. This review delineates the dynamic trajectory of CD8⁺ T-cell exhaustion development in TNBC, provides an update on the latest research advancements in understanding its pathogenesis, and offers insights into potential immunotherapeutic strategies.

CD8+T细胞衰竭已被确定为导致三阴性乳腺癌（TNBC）免疫抑制和免疫逃逸的重要因素。细胞衰竭导致的功能障碍表现为效应能力降低和抑制性受体（IR）持续表达。导致 CD8+ T 细胞衰竭的因素是多方面的，包括外部影响，如 IRs 上调、效应细胞因子减少，以及免疫细胞内部变化，包括转录组改变、表观遗传景观重塑和代谢组转变。TNBC 肿瘤微环境（TME）的改变对 Tex 的影响也是一个重要的考虑因素。CD8+T细胞衰竭（CD8+ Tex）的产生与TNBC患者预后不良和对免疫疗法反应率降低呈正相关，这突出表明迫切需要开发针对CD8+T细胞衰竭机制的新型TNBC免疫治疗策略。本综述描绘了TNBC中CD8+ T细胞衰竭的动态发展轨迹，提供了了解其发病机制的最新研究进展，并对潜在的免疫治疗策略提出了见解。

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引用次数: 0

Modeling bladder cancer in the laboratory: Insights from patient-derived organoids 实验室膀胱癌建模：来自患者器官组织的启示

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-15 DOI: 10.1016/j.bbcan.2024.189199

Zikai Guo , Zhichao Li , Jia Wang , Hongxiao Jiang , Xu Wang , Yangyang Sun , Weiren Huang

Bladder cancer (BCa) is the most common malignant tumor of the urinary system. Current treatments often have poor efficacy and carry a high risk of recurrence and progression due to the lack of consideration of tumor heterogeneity. Patient-derived organoids (PDOs) are three-dimensional tissue cultures that preserve tumor heterogeneity and clinical relevance better than cancer cell lines. Moreover, PDOs are more cost-effective and efficient to cultivate compared to patient-derived tumor xenografts, while closely mirroring the tissue and genetic characteristics of their source tissues. The development of PDOs involves critical steps such as sample selection and processing, culture medium optimization, matrix selection, and improvements in culture methods. This review summarizes the methodologies for generating PDOs from patients with BCa and discusses the current advancements in drug sensitivity testing, immunotherapy, living biobanks, drug screening, and mechanistic studies, highlighting their role in advancing personalized medicine.

膀胱癌（BCa）是泌尿系统最常见的恶性肿瘤。由于缺乏对肿瘤异质性的考虑，目前的治疗方法往往疗效不佳，复发和恶化的风险很高。患者衍生的器官组织（PDOs）是一种三维组织培养物，与癌细胞系相比，它能更好地保持肿瘤的异质性和临床相关性。此外，与患者来源的肿瘤异种移植物相比，PDOs 的培养成本更低，效率更高，同时还能密切反映其源组织的组织和遗传特征。PDOs 的开发涉及样本选择和处理、培养基优化、基质选择和培养方法改进等关键步骤。本综述总结了从 BCa 患者中生成 PDOs 的方法，并讨论了当前在药物敏感性测试、免疫疗法、活体生物库、药物筛选和机理研究方面取得的进展，强调了它们在推进个性化医疗方面的作用。

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引用次数: 0

Belling the “cat”: Wnt/β-catenin signaling and its significance in future cancer therapies 唤醒 "猫"：Wnt/β-catenin 信号转导及其在未来癌症疗法中的意义

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-15 DOI: 10.1016/j.bbcan.2024.189195

Akansha Goyal , Satyajit Laxman Murkute , Sujoy Bhowmik , Chandra Prakash Prasad , Purusottam Mohapatra

The WNT/β-catenin is among one of the most extensively studied cellular signaling pathways involved in the initiation and progression of several deadly cancers. It is now understood that the WNT/β-catenin signaling, during tumor progression operates in a very complex fashion beyond the earlier assumed simple WNT ‘On’ or ‘Off’ mode as it recruits numerous WNT ligands, receptors, transcriptional factors and also cross-talks with other signaling molecules including the noncanonical WNT regulators. WNT/β-catenin signaling molecules are often mutated in different cancers which makes them very challenging to inhibit and sometimes ranks them among the undruggable targets. Furthermore, due to the evolutionary conservation of this pathway, inhibiting WNT/β-catenin has caused significant toxicity in normal cells. These challenges are reflected in clinical trial data, where the use of WNT/β-catenin inhibitors as standalone treatments remains limited. In this review, we have highlighted the crucial functional associations of diverse WNT/β-catenin signaling regulators with cancer progression and the phenotypic switching of tumor cells. Next, we have shed light on the roles of WNT/β-catenin signaling in drug resistance, clonal evolution, tumor heterogeneity, and immune evasion. The present review also focuses on various classes of routine and novel WNT/β-catenin therapeutic regimes while addressing the challenges associated with targeting the regulators of this complex pathway. In the light of multiple case studies on WNT/β-catenin inhibitors, we also highlighted the challenges and opportunities for future clinical trial strategies involving these treatments. Additionally, we have proposed strategies for future WNT/β-catenin-based drug discovery trials, emphasizing the potential of combination therapies and AI/ML-driven prediction approaches. Overall, here we showcased the opportunities, possibilities, and potentialities of WNT/β-catenin signaling modulatory therapeutic regimes as promising precision cancer medicines for the future.

WNT/β-catenin 是研究最广泛的细胞信号通路之一，它与多种致命癌症的发生和发展有关。现在人们已经了解到，在肿瘤进展过程中，WNT/β-catenin 信号以一种非常复杂的方式运行，超出了早先假定的简单 WNT "开 "或 "关 "模式，因为它招募了许多 WNT 配体、受体和转录因子，还与包括非经典 WNT 调节因子在内的其他信号分子发生交叉作用。在不同的癌症中，WNT/β-catenin 信号分子经常发生突变，这使得抑制它们非常具有挑战性，有时甚至将它们列为无法抑制的靶点。此外，由于该通路在进化过程中保持不变，抑制 WNT/β-catenin 会对正常细胞造成严重毒性。这些挑战反映在临床试验数据中，WNT/β-catenin抑制剂作为独立疗法的使用仍然有限。在这篇综述中，我们强调了多种 WNT/β-catenin 信号调节因子与癌症进展和肿瘤细胞表型转换的重要功能关联。接着，我们阐明了 WNT/β-catenin 信号在耐药性、克隆进化、肿瘤异质性和免疫逃避中的作用。本综述还重点介绍了各类常规和新型 WNT/β-catenin 治疗方案，同时探讨了靶向这一复杂通路的调节因子所面临的挑战。根据有关 WNT/β-catenin 抑制剂的多个案例研究，我们还强调了涉及这些疗法的未来临床试验策略所面临的挑战和机遇。此外，我们还提出了未来基于 WNT/β-catenin 的药物发现试验策略，强调了联合疗法和人工智能/ML 驱动的预测方法的潜力。总之，我们在此展示了 WNT/β-catenin 信号调节治疗方案作为未来有前途的精准癌症药物的机遇、可能性和潜力。

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引用次数: 0

Perioperative immunotherapy for patients with EGFR mutant non-small cell lung cancer: Unexpected potential benefits 为表皮生长因子受体突变非小细胞肺癌患者提供围手术期免疫疗法：意想不到的潜在益处。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-14 DOI: 10.1016/j.bbcan.2024.189194

Feifei Teng , Xiao Ju , Zhenhua Gao , Junhao Xu , Yikun Li , Yungang Wang , Bingwen Zou , Jinming Yu

Given that immunotherapy has resulted in a significant overall survival (OS) benefit in advanced-stage disease, it is of notable interest to determine the effectiveness of these agents in early-stage non-small cell lung cancer (NSCLC). The potential exists for the immunotherapeutic approach in early-stage NSCLC to mirror the paradigm seen in advanced NSCLC, wherein survival enhancements have notably benefited the majority of patients. However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial. In the limited studies that included patients with EGFR mutation status, we found unexpected, good survival benefits of perioperative immune checkpoint inhibitors (ICIs) in resectable EGFR-positive NSCLC, which is controversial with those in advanced EGFR-mutant NSCLC. It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones. The subclonality of the resistant subclone is pivotal in therapy response, with tyrosine kinase inhibitors (TKIs) selectively controlling EGFR-mutant cell proliferation and “competitive release” potentially explaining lower pathological responses in adjuvant TKIs trials. This review delves into emerging data on perioperative treatment modalities for early-stage EGFR mutant NSCLC, exploring unique mechanisms and predictive biomarkers to guide perioperative management strategies.

鉴于免疫疗法已使晚期疾病患者的总生存期（OS）明显改善，因此确定这些药物对早期非小细胞肺癌（NSCLC）的疗效就显得尤为重要。早期非小细胞肺癌的免疫治疗方法有可能与晚期非小细胞肺癌的治疗模式相同，晚期非小细胞肺癌患者的生存率明显提高，使大多数患者受益。然而，免疫疗法在早期表皮生长因子受体（EGFR）突变型 NSCLC 中的表现还存在争议。在纳入表皮生长因子受体突变患者的有限研究中，我们发现围手术期免疫检查点抑制剂（ICIs）对可切除的表皮生长因子受体阳性 NSCLC 有意想不到的良好生存获益，而这与晚期表皮生长因子受体突变 NSCLC 的获益存在争议。这可能是因为免疫环境在肿瘤进展过程中发生了免疫抑制的转变。在疾病的早期阶段，抗肿瘤免疫反应的激活障碍较少。就表皮生长因子受体突变肿瘤而言，瘤内遗传异质性可产生治疗敏感亚克隆和耐药亚克隆。耐药亚克隆的亚克隆性对治疗反应至关重要，酪氨酸激酶抑制剂（TKIs）可选择性地控制表皮生长因子受体突变细胞的增殖，而 "竞争性释放 "可能是辅助TKIs试验中病理反应较低的原因。本综述深入探讨了早期表皮生长因子受体突变 NSCLC 围手术期治疗模式的新数据，探索了指导围手术期管理策略的独特机制和预测性生物标志物。

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引用次数: 0

Advancements in therapeutic peptides: Shaping the future of cancer treatment 治疗肽的进步：塑造癌症治疗的未来。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-14 DOI: 10.1016/j.bbcan.2024.189197

Xiaojie Chen , Zhiwei Zhao , Kyle Vaughn Laster , Kangdong Liu , Zigang Dong

In the evolving landscape of cancer treatment, therapeutic peptides are assuming to play an increasingly vital role. Although the number of peptide drugs available for clinical cancer treatment is currently limited, extensive preclinical research is underway, presenting a promising trajectory for the future. The collaborative efforts of natural anti-cancer peptides (ACPs) and synthetic ACPs, propelled by advancements in molecular biology and peptide chemistry, are steering remarkable progress in this domain. We explores the intricate mechanisms underlying the anti-cancer effects of these peptides. The exploration of innovative strategies, including cancer immunotherapy and advanced drug delivery systems, is likely to contribute to the increasing presenceuse of peptide drugs in clinical cancer care. Furthermore, we delve into the potential implications and challenges associated with this anticipated shift, emphasizing the need for continued research and development to unlock the full therapeutic potential of peptide drugs in cancer treatment.

在不断发展的癌症治疗领域，治疗肽正发挥着越来越重要的作用。虽然目前可用于临床癌症治疗的多肽药物数量有限，但广泛的临床前研究正在进行中，为未来的发展提供了良好的前景。在分子生物学和多肽化学进步的推动下，天然抗癌多肽（ACPs）和合成抗癌多肽的共同努力正在这一领域取得显著进展。我们探索了这些肽抗癌作用的复杂机制。对包括癌症免疫疗法和先进给药系统在内的创新策略的探索，很可能会促进肽类药物在临床癌症治疗中的应用。此外，我们还深入探讨了与这一预期转变相关的潜在影响和挑战，强调有必要继续进行研究和开发，以充分释放多肽药物在癌症治疗中的治疗潜力。

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引用次数: 0