Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
HonorHealth Research Institute, Scottsdale, AZ.
Am Soc Clin Oncol Educ Book. 2020 May;40:e275-e291. doi: 10.1200/EDBK_280571.
The rapid expansion of modern cancer immunotherapeutics has led to a dramatic improvement in patient survival and sustained remission for otherwise refractory malignancies. However, a significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. This unpredictability leads to significant side effects, financial costs, and health care burden, with unsatisfactory clinical benefit in the majority of treated patients. Additionally, although ongoing studies and trials investigate the use of multiple biomarkers predictive of patient response or harm, none of these are comprehensive in predicting potential benefit. This unmet need for validated biomarkers is largely secondary to a prohibitive complexity within tumor parenchyma and microenvironment, dynamic clonal and proteomic changes to therapy, heterogenous host immune defects, and varied standardization among sample preparation and reporting. Herein, we discuss current advantages of predictive biomarkers, as well as limitations in their clinical use and application. We also review future directions, ideal characteristics, and trial design needed for proper precision immuno-oncology and biomarker development.
现代癌症免疫疗法的迅速发展，使得患者的生存率和缓解率显著提高，即使是原本难以治疗的恶性肿瘤也是如此。然而，这些当前治疗方法的一个显著局限性是临床反应的不规则性，在检查点抑制中尤为明显。这种不可预测性导致了严重的副作用、经济成本和医疗负担，并且在大多数接受治疗的患者中临床获益并不理想。此外，尽管正在进行的研究和试验探讨了使用多种生物标志物来预测患者的反应或危害，但没有一种方法可以全面预测潜在的获益。这种对经过验证的生物标志物的需求未得到满足，主要是由于肿瘤实质和微环境的复杂性、治疗过程中克隆和蛋白质组的动态变化、宿主免疫缺陷的异质性以及样本准备和报告的标准化程度不同。在此，我们讨论了预测性生物标志物的当前优势，以及其在临床应用中的局限性。我们还回顾了适当的精准免疫肿瘤学和生物标志物开发所需的未来方向、理想特征和试验设计。
