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. Citation Format: Sarah Phillips Suehnholz, Ritika Kundra, Moriah Heller Nissan, Calvin Lu, Nicole Fernandez, Kelly Cavender, Kinisha Gala, Benjamin Preiser, Reshma Ramaiah, John Konecny, Xiang Li, Subhiksha Nandakumar, Kseniya Petrova-Drus, Mark Ewalt, Nikita Mehta, Yonina R. Murciano-Goroff, James Du, Anoop Balakrishnan Rema, Aijazuddin Syed, A. Rose Brannon, Ahmet Dogan, Diana Mandelker, Zsofia K. Stadler, Alexander Drilon, David B. Solit, Ross L. Levine, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Jianjiong Gao, Nikolaus Schultz, Debyani Chakravarty. OncoKB™, MSK’s precision oncology knowledge base: 2025 updates abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2498.
Suehnholz et al. (Fri,) studied this question.