PO.CL07.01 · 临床研究
OncoKB™, MSK's precision oncology knowledge base: 2025 updates
作者与单位
摘要 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.