Kersh Anna E, Ng Spencer, Chang Yun Min, Sasaki Maiko, Thomas Susan N, Kissick Haydn T, Lesinski Gregory B, Kudchadkar Ragini R, Waller Edmund K, Pollack Brian P
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
Emory Vaccine Center, Atlanta, GA.
J Clin Pharmacol. 2018 Jan;58(1):7-24. doi: 10.1002/jcph.1028. Epub 2017 Nov 14.
Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment. Although these 2 modalities were developed and initially used independently, combination regimens are now being tested in clinical trials, underscoring the need to understand how targeted therapies influence immunologic events. Translational studies and preclinical models have demonstrated that targeted therapies can influence immune cell trafficking, the production of and response to chemokines and cytokines, antigen presentation, and other processes relevant to antitumor immunity and immune homeostasis. Moreover, because these and other effects of targeted therapies occur in nonmalignant cells, targeted therapies are being evaluated for use in applications outside of oncology.
目前处于晚期癌症治疗前沿的两种药理学方法,一种是以破坏肿瘤细胞内关键的生长/生存信号通路为核心(通常称为“靶向治疗”),另一种是以增强患者免疫系统产生抗肿瘤反应的能力为核心(免疫治疗)。要使对这两种方法的反应最大化,需要了解特定患者肿瘤中存在的致癌事件以及肿瘤免疫微环境的性质。尽管这两种治疗方式是独立开发并最初单独使用的,但目前正在临床试验中测试联合治疗方案,这突出了了解靶向治疗如何影响免疫事件的必要性。转化研究和临床前模型表明,靶向治疗可影响免疫细胞运输、趋化因子和细胞因子的产生及反应、抗原呈递以及其他与抗肿瘤免疫和免疫稳态相关的过程。此外,由于靶向治疗的这些及其他效应发生在非恶性细胞中,目前正在评估靶向治疗在肿瘤学以外领域的应用。