决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.
这些发现表明,乳腺癌治疗的未来将依赖于针对每个肿瘤和每位患者独特生物学特性设计的个性化、多靶点策略。
乳腺癌治疗随着靶向和多模式策略的发展已取得重大进展,但肿瘤异质性和治疗耐药仍持续限制长期结局。本综述对已确立和新兴的靶向治疗进行了简明而批判性的概述,重点关注耐药机制、药物递送创新和整合治疗策略。已确立的治疗方式,包括内分泌治疗、HER2导向的抗体和抗体-药物偶联物治疗以及化疗,与关键亚型特异性挑战一并进行了总结。新兴靶点如PARP、CDK4/6、WBP2和Trop2,以及针对代谢和肿瘤微环境的策略,就其克服耐药的潜力进行了评估。免疫治疗的进展,包括检查点抑制剂、双特异性抗体和CAR-T细胞疗法,在乳腺癌各亚型中的机制依据和局限性受到审视。基于纳米技术的递送系统、外泌体介导的转运以及多模式预测框架(包括miRNA调控网络)的进展,进一步就其与个体化治疗的相关性进行了评估。总体而言,本综述综合了当前分子见解和治疗创新,为开发更有效、更持久的乳腺癌靶向治疗提供信息。乳腺癌不是一种单一疾病。不同的人发展出不同的肿瘤类型,对治疗的反应方式也不同。由于这种多样性,许多女性仍面临治疗耐药、复发或从当前疗法中获益有限的问题。我们撰写这篇综述旨在帮助读者理解新的科学进展如何重塑乳腺癌治疗,以及这些发展对未来诊疗可能意味着什么。在本文中,我们解释了当今使用的主要治疗方法,包括激素治疗、HER2靶向治疗、化疗、免疫治疗和药物抗体偶联物。我们还描述了重要的新方向,例如作用于DNA修复、细胞周期、肿瘤代谢以及Trop2、WBP2和CDK4/6等蛋白的药物。我们强调了肿瘤周围环境,包括免疫细胞、成纤维细胞、血管和细胞外基质,如何支持治疗或阻碍其疗效。我们还总结了新兴工具,如纳米医学、超声引导药物递送和基于外泌体的疗法。这些技术旨在更精确地递送药物并克服耐药性。我们的综述表明,没有单一疗法足以适用于所有患者。相反,联合靶向药物、免疫治疗、代谢治疗或先进递送系统可能提供更强且更持久的疗效。我们还讨论了使用预测模型和microRNA网络的早期研究,这可能帮助医生为每个人选择最佳疗法。总之,这些发现表明,乳腺癌治疗的未来将依赖于围绕每个肿瘤和每位患者独特生物学特征设计的个性化、多靶点策略。
Breast cancer treatment has advanced substantially with the development of targeted and multimodal strategies, yet tumor heterogeneity and therapeutic resistance continue to limit long-term outcomes. This review provides a concise and critical overview of established and emerging targeted therapies, with emphasis on resistance mechanisms, innovations in drug delivery, and integrative therapeutic approaches. Established modalities, including endocrine therapy, HER2-directed antibody and antibody-drug conjugate therapies, and chemotherapy, are summarized alongside key subtype-specific challenges. Emerging targets such as PARP, CDK4/6, WBP2, and Trop2, as well as metabolic and tumor-microenvironment-oriented strategies, are evaluated for their potential to overcome resistance. Advances in immunotherapy, including checkpoint inhibitors, bispecific antibodies, and CAR-T cell therapies, are examined with attention to mechanistic rationale and limitations across breast cancer subtypes. Progress in nanotechnology-based delivery systems, exosome-mediated transport, and multimodal predictive frameworks, including miRNA regulatory networks, is further assessed for its relevance to personalized treatment. Overall, this review synthesizes current molecular insights and therapeutic innovations to inform the development of more effective and durable targeted treatments for breast cancer. Breast cancer is not a single disease. Different people develop different tumor types, which respond in different ways to treatment. Because of this diversity, many women still face treatment resistance, relapse, or limited benefit from current therapies. We wrote this review to help readers understand how new scientific advances are reshaping breast cancer treatment and what these developments may mean for future care. In this article, we explain the major treatment approaches used today, including hormone-based therapy, HER2-targeted therapy, chemotherapy, immunotherapy, and drug antibody combinations. We also describe important new directions, such as medicines that act on DNA repair, the cell cycle, tumor metabolism, and proteins like Trop2, WBP2, and CDK4/6. We highlight how the tumor s surrounding environment, including immune cells, fibroblasts, blood vessels, and the extracellular matrix, can either support treatment or impede its effectiveness. We also summarize emerging tools such as nanomedicine, ultrasound-guided drug delivery, and exosome-based therapies. These technologies aim to deliver drugs more precisely and overcome resistance. Our review shows that no single therapy is enough for all patients. Instead, combining targeted drugs, immunotherapy, metabolic treatments, or advanced delivery systems may offer stronger and longer-lasting effects. We also discuss early research using prediction models and microRNA networks, which may help doctors choose the best therapy for each person. Together, these findings suggest that the future of breast cancer treatment will rely on personalized, multi-target strategies designed around the unique biology of each tumor and each patient.
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