ArticleCancer discovery2021
TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors.
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Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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Who cites it
24 citing papers in PubMed, 69 citations in OpenAlex.
- Not all NTRK fusions in mesenchymal neoplasia are driver events: implications on classification and targeted therapy.The journal of pathology. Clinical research · 2026Article
- AcquiredJTO clinical and research reports · 2026Article
- Kinase Inhibitors for Targeted Cancer Therapy.Current topics in medicinal chemistry · 2026Review
- Case report: Successful use of MEK inhibitors as an adjuvant approach in the treatment of pediatric MAP4-RAF1 fusion-positive solid tumor.NPJ precision oncology · 2025Article
- Responsiveness of different MET tumour alterations to type I and type II MET inhibitors.Clinical and translational medicine · 2025Article
- Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents.British journal of cancer · 2024Article
- Patient-Derived-Xenografts in Mice: A Preclinical Platform for Cancer Research.Cold Spring Harbor perspectives in medicine · 2024Review
- Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.JCO precision oncology · 2024Article
- Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib.Acta pharmaceutica Sinica. B · 2024Review
- Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Current landscape of tropomyosin receptor tyrosine kinase inhibitors.Future medicinal chemistry · 2024Article
- The FLT3American journal of hematology · 2023Article
- Response to Repotrectinib After Development ofJCO precision oncology · 2023Article
- Rare molecular subtypes of lung cancer.Nature reviews. Clinical oncology · 2023Review
- Precision oncology using organoids of a secretory carcinoma of the salivary gland treated with TRK-inhibitors.Oral oncology · 2023Article
- Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China.Thoracic cancer · 2022Article
- JND4135, a New Type II TRK Inhibitor, Overcomes TRK xDFG and Other Mutation Resistance In Vitro and In Vivo.Molecules (Basel, Switzerland) · 2022Article
- TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults.Cancer genetics · 2022Review
- NTRK insights: best practices for pathologists.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Review
- NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
34 authors at 6 institutions in 4 countries.
Emiliano CoccoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. scaltrim@mskcc.org coccoe@mskcc.org chandra@bii.a-star.edu.sg venturaa@mskcc.org drilona@mskcc.org.
Ji Eun Lee *Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-9187-8641
Srinivasaraghavan Kannan *Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore.ORCID 0000-0002-9539-5249
Alison M Schram *Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-6070-2413
Helen H WonCenter for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-5237-7529
Sophie ShifmanHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Amanda KulickAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
Laura BaldinoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Eneda ToskaHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Amaia Arruabarrena-AristorenaHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-1636-3944
Srushti KittaneHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Fan WuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-3960-320X
Yanyan CaiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Sabrina ArenaDepartment of Oncology, University of Torino, Candiolo, Torino, Italy.ORCID 0000-0002-1318-2494
Benedetta MussolinCandiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.ORCID 0000-0001-5723-5685
Ram KannanCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-9539-5249
Neil VasanHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Alexander N GorelickHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-6736-8246
Michael F BergerHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Ofra NovoplanskyThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.ORCID 0000-0002-1239-7856
Sankar JagadeeshanThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.ORCID 0000-0002-3778-8757
Yi LiaoDepartment of Drug Discovery, Moffitt Cancer Center, Tampa, Florida.
Uwe RixDepartment of Drug Discovery, Moffitt Cancer Center, Tampa, Florida.ORCID 0000-0002-8242-2770
Sandra MisaleMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Barry S TaylorDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Alberto BardelliDepartment of Oncology, University of Torino, Candiolo, Torino, Italy.
Jaclyn F HechtmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
David M HymanDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Moshe ElkabetsThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.ORCID 0000-0003-3634-9098
Elisa de StanchinaAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
Chandra S VermaBioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore. scaltrim@mskcc.org coccoe@mskcc.org chandra@bii.a-star.edu.sg venturaa@mskcc.org drilona@mskcc.org.
Andrea VenturaCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York. scaltrim@mskcc.org coccoe@mskcc.org chandra@bii.a-star.edu.sg venturaa@mskcc.org drilona@mskcc.org.
Alexander DrilonDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. scaltrim@mskcc.org coccoe@mskcc.org chandra@bii.a-star.edu.sg venturaa@mskcc.org drilona@mskcc.org.ORCID 0000-0001-6806-9061
Maurizio ScaltritiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. scaltrim@mskcc.org coccoe@mskcc.org chandra@bii.a-star.edu.sg venturaa@mskcc.org drilona@mskcc.org.ORCID 0000-0002-5522-1447
Memorial Sloan Kettering Cancer Center · USBen-Gurion University of the Negev · ILAgency for Science, Technology and Research · SGMoffitt Cancer Center · USTorino e-district · ITCandiolo Cancer Institute · IT
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MInvestigational Cancer Therapeutics Training Program (ICTTP)T32CA009207 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Omar Abdel-Wahab, Alexander Drilon · 1985 to 2026
$13.7MUnderstanding tumor addiction to TRK fusions and sensitivity to TRK inhibitionR01CA226864 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DRILON, ALEXANDER, VENTURA, ANDREA · 2018 to 2021
$2.5MHarnessing beneficial off-target effects of kinase inhibitors in lung cancerR01CA181746 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RIX, UWE · 2015 to 2019
$2.3MTranslational Research in Oncology Training ProgramT32CA160001 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SAWYERS, CHARLES L. · 2011 to 2020
$2.0MUnderstanding Long Tail Driver Mutations in CancerR01CA204749 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SCHULTZ, NIKOLAUS · 2017 to 2021
$2.0MHorizontal Bore 9.4T Magnet for MRIS10OD023669 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI KOUTCHER, JASON ARTHUR · 2017 to 2017
$600kNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA181746NCI NIH HHS R01 CA204749NCI NIH HHS R01 CA226864NCI NIH HHS T32 CA009207NCI NIH HHS T32 CA160001NIH HHS S10 OD023669
Abstract
On-target resistance to next-generation TRK inhibitors in TRK fusion-positive cancers is largely uncharacterized. In patients with these tumors, we found that TRK xDFG mutations confer resistance to type I next-generation TRK inhibitors designed to maintain potency against several kinase domain mutations. Computational modeling and biochemical assays showed that TRKA
Indexed as
NeoplasmsReceptor, trkAHumansMutationOncogenesProtein Kinase InhibitorsProtein Kinase InhibitorsReceptor, trkA
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