Abstract 99: Evolution of OncoKB, a precision oncology knowledgebase

作者：Sarah Phillips Suehnholz, Ritika Kundra, Hongxin Zhang, Shaleigh A. Smith, Moriah H. Nissan, Yifu Yao, Lindsay M. LaFave, Kinisha P. Gala, Linde A. Miles, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Ahmet Zehir, Aijaz Syed, Julia E. Rudolph, Paul J. Sabbatini, Ross L. Levine, Ahmet Doǧan, Jianjiong Gao, David B. Solit, Nikolaus D. Schultz, Debyani Chakravarty · 发表于：Cancer Research · 年份：2021 · DOI：10.1158/1538-7445.am2021-99 · 被引用次数：3 · 研究领域：Cancer Genomics and Diagnostics、Radiomics and Machine Learning in Medical Imaging、Ferroptosis and cancer prognosis

Abstract Genomic sequencing of tumors is a routine part of cancer patient care. To address the need for a comprehensive resource that annotates the oncogenic effects and clinical actionability of somatic alterations in cancer, we developed OncoKB, a precision oncology knowledgebase. Since its introduction in 2016, OncoKB has grown to include annotations for >500 alterations in 682 genes. This includes 42 Level 1 genes (included in the FDA drug label), 12 Level 2 genes (included in the NCCN guidelines), and 29 Level 3A genes (predictive of drug response in well-powered clinical studies). We evaluated changes in the clinical actionability landscape and evolution of the OncoKB annotation rules and processes by comparing the AACR Project GENIE cohort (v8.1) annotated with the OncoKB version from February 2018 to that from November 2020. Even within a short window of time, this comparison reveals a significant shift of the proportion of samples that harbor a standard care alteration (Level 1 and 2), increasing from ~9% in 2018 to ~24% in 2020, and a Level 3A alteration, decreasing from ~11% to ~5%. This shift is partially attributable to the FDA approval of a PI3K inhibitor in PIK3CA-mutant ER+/HER2- breast cancer, approval of RAF inhibitors in BRAF V600E mutant anaplastic thyroid cancer and colorectal cancer, approval of NTRK-inhibitors in NTRK fusion-positive solid tumors, FGFR-inhibitor approval in FGFR2 fusion-positive bladder cancer and cholangiocarcinoma, RET-inhibitor appro...