NTRK fusion molecules and uses thereof
Inventors
DARCY, Christopher • CLASSON, Anthony • SOKOL, Ethan Samuel • Liu, Xin • GORNSTEIN, Erica • Rosenzweig, Mark • ERBACH, Rachel
Assignees
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Publication Number
US-12649952-B2
Publication Date
2026-06-09
Expiration Date
Abstract
NTRK fusion molecules, detection reagents, and uses and kits for evaluating, identifying, assessing, and/or treating a subject having a cancer are disclosed.
Core Innovation
The disclosure describes neurotrophic receptor tyrosine kinase (NTRK) fusion nucleic acids and polypeptides, including NTRK1, NTRK2, and NTRK3 gene fusions such as MEX3A-NTRK1 and CARM1-NTRK3, which retain kinase domains and exhibit elevated or constitutive kinase activity. It provides reagents, kits, probes, primers, genomic breakpoint ranges, and fusion-expressing cells for detecting and characterizing alterations in tumor, FFPE tissue, blood, cfDNA, and ctDNA samples across various cancer contexts.
The claim provides a method of treating or delaying progression of cancer by detecting an NTRK fusion nucleic acid molecule or polypeptide in a sample from an individual with cancer. The detected fusion nucleic acid molecule encodes or is encoded by specified nucleotide sequences. The method further comprises administering to the individual an effective amount of a treatment comprising a kinase inhibitor.
Claims Coverage
The provided relevant claims identify one independent claim containing two inventive features.
Detection of an NTRK fusion
Detecting a neurotrophic receptor tyrosine kinase (NTRK) fusion nucleic acid molecule or an NTRK fusion polypeptide in a sample from an individual with cancer, wherein the NTRK fusion nucleic acid molecule encodes or is encoded by the nucleotide sequence of any one of SEQ ID NOs: 5, 11, 67, 71, and 118.
Administration of a kinase-inhibitor treatment
Administering to the individual an effective amount of a treatment comprising a kinase inhibitor to treat or delay progression of cancer.
The independent claim covers cancer treatment or delayed cancer progression based on the detection of a specified NTRK fusion nucleic acid molecule or polypeptide followed by administration of a kinase-inhibitor treatment.
Stated Advantages
The claimed method is directed to treating or delaying progression of cancer.
Documented Applications
Treating or delaying progression of cancer in an individual whose sample contains an NTRK fusion by administering a kinase-inhibitor treatment, alone or in combination with other therapeutic agents or methyltransferase inhibitors.
Detecting and characterizing NTRK fusion molecules in tumor, FFPE tissue, blood, cfDNA, and ctDNA samples using fusion-specific reagents, assays, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR).
Fusion-based cancer assessment, screening result evaluation, assessment of clinical-trial eligibility, and generating personalized cancer treatment reports with prognostic and therapeutic information.
Treatment of specific associated cancers, including ovarian carcinosarcoma and melanoma, such as vaginal melanoma.
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