Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research.
Translational Clinical Oncology, Novartis Institutes for BioMedical Research.
Nat Rev Cancer. 2017 May;17(5):286-301. doi: 10.1038/nrc.2017.17. Epub 2017 Mar 24.
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.
在过去的 25 年中，癌症治疗学的研究主要集中在两个截然不同的研究方向上。一种方法是努力理解肿瘤发生的内在细胞自主性、遗传驱动因素，这导致了临床上重要的靶向药物的开发，这些药物在遗传定义的患者群体中产生了深刻但往往不可持久的肿瘤反应。在第二种平行方法中，对保护性肿瘤免疫机制的探索提供了几种治疗策略——最显著的是“免疫检查点”抗体，它逆转了 T 细胞功能的负调节剂——这些策略在各种肿瘤类型的亚组患者中实现了持久的临床反应。这些潜在互补研究领域的整合为改善癌症治疗提供了新的机会。靶向和免疫治疗已经改变了几种恶性肿瘤的标准治疗方法。然而，更多地了解靶向治疗以及常规化疗和放疗对诱导抗肿瘤免疫的影响，将有助于推进联合策略的设计，提高患者完全和持久临床反应的速度。
