海报库PosterKeep
PO.CL07.01 · 临床研究

OncoKB™，MSK的精准肿瘤学知识库：2025年更新

OncoKB™, MSK's precision oncology knowledge base: 2025 updates

海报缩略图：OncoKB™，MSK的精准肿瘤学知识库：2025年更新
编号 2498 展板 5 时间 4/20 09:00–12:00 区域 Section 43 主讲 Moriah Nissan, PhD
分会场 Data-Driven Approaches to Precision Oncology
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作者与单位 Authors & Affiliations

Sarah Phillips Suehnholz1, Ritika Kundra1, Moriah Heller Nissan2, Calvin Lu1, Nicole Fernandez1, Kelly Cavender1, Kinisha Gala1, Benjamin Preiser1, Reshma Ramaiah1, John Konecny1, Xiang Li1, Subhiksha Nandakumar3, Kseniya Petrova-Drus1, Mark Ewalt1, Nikita Mehta1, Yonina R. Murciano-Goroff1, James Du1, Anoop Balakrishnan Rema1, Aijazuddin Syed1, A. Rose Brannon1, Ahmet Dogan1, Diana Mandelker1, Zsofia K. Stadler1, Alexander Drilon1, David B. Solit1, Ross L. Levine4, Maria E. Arcila1, Marc Ladanyi1, Michael F. Berger1, Jianjiong Gao1, Nikolaus Schultz1, Debyani Chakravarty1

1Memorial Sloan Kettering Cancer Center, New York, NY,2Memorial Sloan Kettering Cancer Center, San Diego, CA,3Memorial Sloan Kettering Cancer Center, Ann Arbor, MI,4Assistant Member, Human Onc. Pathogenesis Prog., Memorial Sloan Kettering Cancer Center, New York, NY

摘要 Abstract

中文摘要
OncoKB™是由纪念斯隆凯特琳癌症中心（MSK）开发的精准肿瘤学知识库，为950个癌症相关基因中的>8,000种体细胞改变提供经专家审阅的生物学功能和临床可操作性解读。它仍是唯一部分获得美国FDA认可的体细胞癌症变异知识库。在MSK，OncoKB™迄今已注释了超过100,000份患者测序报告，并支持数千名cBioPortal日活用户满足其变异解读需求。此外，全球数千名用户正在利用OncoKB™注释和解读癌症变异。OncoKB™可通过www.oncokb.org公开访问。它可免费用于学术研究，临床和商业用途需要付费许可。 OncoKB™根据支持某改变作为特定癌症亚型药物反应预测性生物标志物的证据水平对改变进行分类。迄今为止，OncoKB™包括58个1级基因以及MSI-H和TMB-H（纳入FDA药物标签）、6个2级基因（纳入专业指南）、10个3A级基因（在效力充足的临床研究中预测反应）、1个4级基因（基于令人信服的生物学证据预测反应）以及12个R1/R2耐药基因。 2025年，基于FDA批准dordaviprone用于H3F3A、H3C2和H3C3 K28M突变型弥漫性中线胶质瘤，OncoKB™新增了3个1级生物标志物。基于FDA分别批准revumenib和avutometinib+defactinib，OncoKB™还将急性髓系白血病中的NPM1突变和低级别浆液性卵巢癌中的KRAS突变提升至1级。随着FDA批准datopotamab deruxtecan用于EGFR突变型非小细胞肺癌（NSCLC），多种EGFR改变（包括19号外显子框内插入和激酶结构域重复）也被提升至1级。NCCN胰腺癌和NSCLC指南分别为FGFR1/2融合阳性和FGFR1/3突变肿瘤增加了erdafitinib，将这些确立为OncoKB™ 2级生物标志物。同样，NCCN小肠腺癌指南为KRAS G12C突变肿瘤列入了sotorasib和adagrasib，NCCN乳腺癌指南为携带ERBB2突变的肿瘤列入了neratinib+trastuzumab+fulvestrant，在这些适应症中也被指定为2级状态。总之，2025年共有3个新的具有临床可操作性的生物标志物以及针对现有分级生物标志物的20种后续精准肿瘤学疗法被纳入OncoKB™。 OncoKB™已开始注释胚系变异，以实现对配对肿瘤-正常组织测序结果的整合解读。其他正在进行的工作包括更新诊断和预后生物标志物注释、临床试验匹配模块，以及试点基于AI的整理工作流程，以扩展OncoKB™对通过全基因组或转录组测序及免疫组化检测到的生物标志物的注释。
查看英文原文 English abstract
OncoKB™, a precision oncology knowledgebase developed at Memorial Sloan Kettering Cancer Center (MSK), provides expert-reviewed interpretations of the biological function and clinical actionability for >8,000 somatic alterations in 950 cancer-associated genes. It remains the only somatic cancer variant knowledgebase partially recognized by the U.S. FDA. At MSK, OncoKB™ has annotated over 100,000 patient sequencing reports so far and it supports thousands of cBioPortal daily users for their variant interpretation needs. In addition, thousands of users globally are utilizing OncoKB™ for annotating and interpreting cancer variants. OncoKB™ is publicly accessible at www.oncokb.org . It can be used for free for academic research and requires a fee-based license for clinical and commercial use. OncoKB™ classifies alterations based on the level of evidence supporting the alteration as a predictive biomarker of drug response in a specific cancer subtype. To date OncoKB™ includes 58 Level 1 genes as well as MSI-H and TMB-H (included in the FDA drug label), 6 Level 2 genes (included in professional guidelines), 10 Level 3A genes (predictive of response in well-powered clinical studies), 1 Level 4 gene (predictive of response based on compelling biological evidence), and 12 R1/R2 resistance genes. In 2025, OncoKB™ added 3 novel level 1 biomarkers based on the FDA approval of dordaviprone in H3F3A, H3C2, and H3C3 K28M -mutant diffuse midline glioma. OncoKB™ also promoted NPM1 mutations in acute myeloid leukemia and KRAS mutations in low-grade serous ovarian cancer to level 1 based on FDA approvals of revumenib and avutometinib + defactinib, respectively. Multiple EGFR alterations, including exon 19 in-frame insertions and kinase domain duplications, were also elevated to level 1 following FDA approval of datopotamab deruxtecan for EGFR mutant non-small cell lung cancer (NSCLC). NCCN guidelines for pancreatic cancer and NSCLC added erdafitinib for FGFR1/2 fusion-positive and FGFR1/3 -mutant tumors, respectively, establishing these as OncoKB™ level 2 biomarkers. Similarly, the NCCN small bowel adenocarcinoma guidelines listed sotorasib and adagrasib for KRAS G12C-mutant tumors, and the NCCN breast cancer guidelines listed neratinib + trastuzumab + fulvestrant for tumors with ERBB2 mutations, also designating level 2 status in these indications. In sum, 3 novel clinically actionable biomarkers and 20 follow-on precision oncology therapies for existing leveled biomarkers were incorporated into OncoKB™ in 2025. OncoKB™ has started annotating germline variants to enable integrated interpretation of paired tumor-normal sequencing results. Other ongoing efforts include updates to diagnostic and prognostic biomarker annotations, a clinical trial matching module, and piloting AI-based curation workflows to expand OncoKB™ annotation for biomarkers detected by whole genome or transcriptome sequencing and immunohistochemistry.
利益披露 Disclosure
S. Phillips Suehnholz, None.. R. Kundra, None.. M. H. Nissan, None.. C. Lu, None.. N. Fernandez, None. K. Cavender, Vertex Stock. Exelixis Stock. Eli Lilly Stock. Novartis Stock. K. Gala, Urgent Stock. Allogene Stock. Illumina Stock. B. Preiser, None.. R. Ramaiah, None. J. Konecny, Regeneron Other, Employer of spouse. X. Li, None.. K. Petrova-Drus, None. M. Ewalt, Arima Genomics Other, Professional services and activities. Pillar Biosciences Professional services and activities. N. Mehta, None. Y. R. Murciano-Goroff, AbbVie ), Gift, Other, Professional Services and Activities. Revolution Medicines Other, Professional Services and Activities. Wolters Kluwer Other Intellectual Property. AstraZeneca Travel, Gift. Elucida Oncology ). Loxo Oncology/Eli Lilly ), Travel, Gift. Mirati Therapeutics ). Bristol Myers Squibb/E.R. Squibb & Sons ). Taiho Oncology ), Gift. Hengrui USA/Jiangsu Hengrui Pharmaceuticals ). Luzsana Biotechnology ). Endeavor Biomedicines ), Gift. Erasca ). Arvinas ), Gift. J. Du, None.. A. Balakrishnan Rema, None.. A. Syed, None. A. Brannon, Johnson & Johnson Other, Equity. SOPHiA GENETICS S.A. Other Intellectual Property. A. Dogan, None. D. Mandelker, AstraZeneca Other, Professional Services and Activities (Uncompensated). AstraZeneca UK Limited Other, Professional Services and Activities. Z. K. Stadler, SOPHiA GENETICS S.A. Other Intellectual Property. UptoDate Professional Services and Activities. A. Drilon, AnHeart Therapeutics Other, Professional Services and Activities. Bayer Other, Professional Services and Activities. Boundless Bio Other, Professional Services and Activities. Bristol-Myers Squibb Other, Professional Services and Activities. Conexiant (BroadcastMed) Other, Professional Services and Activities. EcoR1 Capital Other, Professional Services and Activities. IDEOlogy Health Other, Professional Services and Activities. Loxo Oncology Other, Professional Services and Activities. MBrace Therapeutics Other, Equity. Medscape Other, Professional Services and Activities. MJH Life Sciences Other, Professional Services and Activities. Northwell Health Other, Professional Services and Activities. Nuvalent Other, Professional Services and Activities. OncLive Other, Professional Services and Activities. Total CME Other, Professional Services and Activities. Treeline Biosciences Other, Equity; Professional Services and Activities. Zymeworks Other, Professional Services and Activities. D. B. Solit, Antares Therapeutics Other, Equity. BridgeBio Other, Professional Services and Activities. Corramedical Other, Equity. Elsie Biotechnologies Other, Equity; Professional Services and Activities. Fog Pharmaceuticals Other, Professional Services and Activities. Fore Biotherapeutics Other, Equity; Professional Services and Activities. Function Oncology Other, Equity; Professional Services and Activities. Meliora Therapeutics Other, Professional Services and Activities. Paige.AI Other, Professional Services and Activities. Pfizer Other, Professional Services and Activities. Pyramid Biosciences Other, Equity; Professional Services and Activities. Scorpion Therapeutics Other, Equity; Professional Services and Activities. R. L. Levine, Ajax Therapeutics Other, Equity; Fiduciary Role / Position; Intellectual Property Rights; Professional Services and Activities (Uncompensated). Auron Therapeutics Other, Equity; Professional Services and Activities (Uncompensated). C4 Therapeutics Other, Professional Services and Activities. Genome Quebec Other, Professional Services and Activities. Jubilant Therapeutics Other, Professional Services and Activities. Kurome Therapeutics Other, Equity; Professional Services and Activities. Mission Bio Other, Equity; Professional Services and Activities. Prelude Therapeutics Other, Equity; Professional Services and Activities (Uncompensated). Qiagen Other, Equity; Fiduciary Role / Position. Scorpion Therapeutics Other, Equity; Professional Services and Activities. Stelexis Therapeutics Other, Equity; Professional Services and Activities (Uncompensated). Syndax Other, Equity. Zentalis Pharmaceuticals Equity; Professional Services and Activities (Uncompensated). M. E. Arcila, AstraZeneca Professional services and activities. SOPHiA GENETICS S.A. Other Intellectual Property. M. Ladanyi, Gilead Sciences Professional Services and Activities. Merck & Co Professional Services and Activities. Paige.AI Other, Equity; Professional Services and Activities (Uncompensated). SOPHiA GENETICS S.A. Other Intellectual Property. M. F. Berger, AstraZeneca Other, Professional Services and Activities. Paige.AI Professional Services and Activities. SOPHiA GENETICS S.A. Other Intellectual Property. J. Gao, Manifold AI Other, Consulting or Advisory Role. N. Schultz, None.. D. Chakravarty, None.

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