Division of Hematology & Medical Oncology, Oregon Health & Science University/Knight Cancer Institute, Portland, Oregon.
Division of Oncology 3, Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food & Drug Administration, Silver Spring, Maryland.
Cancer Discov. 2021 Sep;11(9):2139-2144. doi: 10.1158/2159-8290.CD-21-0554.
In recent years, there has been remarkable progress in our understanding of cancer biology, host responses, and the concept of precision oncology. These advances have focused attention on biomarker-driven, tissue-agnostic drug development strategies. The recent approvals by the FDA of pembrolizumab for the treatment of unresectable or metastatic, microsatellite instability-high or deficient mismatch repair solid tumors, and more recently for the treatment of tumor mutational burden-high tumors; and of larotrectinib and entrectinib for the treatment of neurotrophic tyrosine kinase () fusion-positive solid tumors, have further heightened interest in target-driven as opposed to histology-driven drug development. Herein, we focus on tissue-agnostic clinical drug development with an understanding of target modulation in the context of histology. The use of molecular genetics and biomarker-driven strategies rather than traditional histology based on organ of origin has reinforced the concept of tissue-agnostic drug development. Recent approvals in the United States, Europe, Japan, Australia, and other regions have further heightened interest in target-driven as opposed to histology-driven drug development.
近年来，我们对癌症生物学、宿主反应和精准肿瘤学概念的理解取得了显著进展。这些进展使人们关注基于生物标志物的、组织不可知的药物开发策略。最近，FDA 批准 pembrolizumab 用于治疗不可切除或转移性、微卫星不稳定高或错配修复缺陷型实体瘤，以及最近用于治疗肿瘤突变负担高的肿瘤；larotrectinib 和 entrectinib 用于治疗神经营养酪氨酸激酶（）融合阳性实体瘤，这进一步提高了人们对靶向驱动而非组织学驱动药物开发的兴趣。在此，我们重点关注组织不可知的临床药物开发，并了解组织学背景下的靶点调节。分子遗传学和基于生物标志物的策略的使用，而不是基于起源器官的传统组织学，强化了组织不可知药物开发的概念。最近在美国、欧洲、日本、澳大利亚和其他地区的批准进一步提高了人们对靶向驱动而非组织学驱动药物开发的兴趣。
