文章：

靶向和常规肿瘤治疗与免疫治疗联合的前景

Prospects for combining targeted and conventional cancer therapy with immunotherapy

原文发布日期：2017-03-24

DOI: 10.1038/nrc.2017.17

类型: Review Article

开放获取: 否

要点：

1. The largely independent research fields of targeted and immune-based cancer therapies are integrating.
2. Research is focused on understanding the impact that targeted and conventional cancer therapies (chemotherapy and radiation) have on the generation of an antitumour immune response. Protective tumour immunity is thought to require innate immune stimulation, a robust cytotoxic T cell response and overcoming an immunosuppressive tumour microenvironment.
3. Insights into the effects of targeted therapies, along with conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical responses in patients.
4. Immune checkpoint inhibitors are emerging as a backbone of cancer therapy and are being combined in clinical trials with many targeted agents.
5. Key future challenges to developing rational combinations include continuing to understand the impact that all cancer therapeutics have on patients' immune systems, optimizing the therapeutic window of treatment through appropriate dosing and temporal sequencing, and prioritizing the rapidly growing number of combination therapy trials.

要点翻译：

1. 靶向治疗和免疫疗法这两个很大程度上独立发展的癌症研究领域正在相互融合。
2. 当前研究重点在于理解靶向治疗与常规癌症治疗（化疗和放疗）对激发抗肿瘤免疫反应的影响。保护性肿瘤免疫被认为需要先天免疫刺激、强大的细胞毒性T细胞反应以及克服免疫抑制性肿瘤微环境。
3. 深入理解靶向疗法及传统化疗、放疗对诱导抗肿瘤免疫的作用，将有助于推进联合治疗方案的设计，从而提高患者完全缓解率和长期临床疗效。
4. 免疫检查点抑制剂正逐渐成为癌症治疗的基石，在临床试验中正与多种靶向药物开展联合应用。
5. 未来开发合理联合方案面临的关键挑战包括：持续探究所有癌症疗法对患者免疫系统的影响，通过精准给药和时间序贯优化治疗窗口，并对快速增长中的联合疗法试验进行优先级排序。

英文摘要：

Over the past 25 years, research in cancer therapeutics has largely focused on two distinct lines of enquiry. In one approach, efforts to understand the underlying cell-autonomous, genetic drivers of tumorigenesis have led to the development of clinically important targeted agents that result in profound, but often not durable, tumour responses in genetically defined patient populations. In the second parallel approach, exploration of the mechanisms of protective tumour immunity has provided several therapeutic strategies — most notably the 'immune checkpoint' antibodies that reverse the negative regulators of T cell function — that accomplish durable clinical responses in subsets of patients with various tumour types. The integration of these potentially complementary research fields provides new opportunities to improve cancer treatments. Targeted and immune-based therapies have already transformed the standard-of-care for several malignancies. However, additional insights into the effects of targeted therapies, along with conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical response in patients.

摘要翻译： 

过去25年里，癌症治疗研究主要沿着两条不同的探索路线展开。第一种方法致力于揭示肿瘤发生中细胞自主性、遗传驱动的机制，由此催生出一批具有临床价值的靶向药物，在基因特征明确的病人群体中可产生显著却常难持久的肿瘤缓解。第二种并行的策略则聚焦于保护性肿瘤免疫的机制解析，带来了若干治疗手段——最突出的是“免疫检查点”抗体，它们解除T细胞功能的负向调控，在多种肿瘤类型的部分患者中实现了持久的临床应答。将这两条潜在互补的研究路线融合，为提升癌症治疗提供了新的契机。靶向与免疫疗法已使多种恶性肿瘤的标准治疗发生变革。然而，进一步阐明靶向治疗以及传统化疗和放疗诱导抗肿瘤免疫的效应，将有助于设计联合策略，提高患者完全且持久临床缓解的比例。

原文链接：

Prospects for combining targeted and conventional cancer therapy with immunotherapy