Khagi Yulian, Kurzrock Razelle, Patel Sandip Pravin
Center for Personalized Cancer Therapy, Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA, 92093, USA.
Cancer Metastasis Rev. 2017 Mar;36(1):179-190. doi: 10.1007/s10555-016-9652-y.
With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer. Though FDA-approved indications for use of some of these novel agents depend on current protein-based programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) assays, detection methods come with several caveats. Additional predictive tools must be interrogated to discern responders from non-responders. Some of these include measurement of microsatellite instability, PD-L1 amplification, cluster of differentiation 8 (CD8) infiltrate density, and tumor mutational burden. This review serves to synthesize biomarker detection at the DNA, RNA, and protein level to more accurately forecast benefit from these novel agents.
随着靶向治疗的出现，多种组织学类型的癌症治疗发生了变革。免疫检查点阻断使得在广泛的恶性肿瘤中利用免疫细胞与肿瘤细胞之间的受体-配体相互作用成为可能。然而，健康组织中的毒性可能会限制这些药物的使用。免疫检查点阻断已被批准用于晚期黑色素瘤、肾细胞癌、非小细胞肺癌、复发难治性霍奇金淋巴瘤和尿路上皮癌。尽管美国食品药品监督管理局（FDA）批准使用其中一些新型药物的适应症取决于当前基于蛋白质的程序性死亡1（PD-1）和程序性死亡配体1（PD-L1）检测，但检测方法存在一些注意事项。必须研究其他预测工具以区分反应者和无反应者。其中一些包括微卫星不稳定性的测量、PD-L1扩增、分化簇8（CD8）浸润密度和肿瘤突变负荷。本综述旨在综合DNA、RNA和蛋白质水平的生物标志物检测，以更准确地预测这些新型药物的疗效。
