NTRK1 fusion molecules and uses thereof
Inventors
Hawryluk, Matthew J. • Lipson, Doron • Miller, Vincent A. • Stephens, Philip James
Assignees
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Publication Number
US-11578372-B2
Publication Date
2023-02-14
Expiration Date
Abstract
Novel NTRK1 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 relates to methods of treating cancer by detecting an MPRIP-NTRK1 fusion in a subject and administering an effective amount of a kinase inhibitor. The fusion includes exon 21 of MPRIP fused in-frame with exon 12 of NTRK1, retaining the NTRK1 tyrosine kinase domain, or specified intronic forms. Described materials and methods for characterizing the fusion include allele-specific primers, FISH, sequencing, protein assays, and diagnostic kits.
The MPRIP-NTRK1 fusion exhibits constitutive TRKA kinase activity and oncogenic effects in lung adenocarcinoma and cancer. TRK-active kinase inhibitors suppress fusion signaling and cell growth in preclinical models to treat fusion-positive cancer. Treatment methods encompass identifying the fusion to inform cancer-treatment selection and administering an effective amount of a kinase inhibitor to the subject.
Claims Coverage
The patent claims comprise two inventive features across two independent claims directed to fusion-detection-based cancer treatments.
Detection of specified MPRIP-NTRK1 fusion forms and kinase-inhibitor treatment of lung cancer
The claim covers detecting an MPRIP-NTRK1 fusion comprising a nucleic acid molecule with a fusion between intron 21 of MPRIP and intron 11 of NTRK1, an in-frame fusion between exon 21 of MPRIP and exon 12 of NTRK1, or a polypeptide comprising the corresponding encoded exon fusion in a subject having lung cancer, and administering an effective amount of a kinase inhibitor.
Detection of specified MPRIP-NTRK1 fusion forms and kinase-inhibitor treatment of cancer
The claim covers detecting an MPRIP-NTRK1 fusion comprising the specified intronic or in-frame exonic nucleic-acid forms, or a polypeptide comprising the encoded exon 21 MPRIP-exon 12 NTRK1 fusion in a subject having cancer, and administering an effective amount of a kinase inhibitor.
Both independent claims center on targeted treatment of lung cancer or cancer generally by administering an effective amount of a kinase inhibitor following the detection of specified intronic, exonic, or polypeptide forms of an MPRIP-NTRK1 fusion.
Stated Advantages
TRK inhibitors suppress MPRIP-NTRK1 fusion signaling and cell growth in preclinical models.
Administering a kinase inhibitor treats lung cancer or cancer in the subject.
Documented Applications
Detection of MPRIP-NTRK1 fusions in subjects with cancer, including lung cancer, using allele-specific primers, FISH, sequencing, or protein assays to inform treatment selection.
Treatment of subjects having MPRIP-NTRK1 fusion-positive cancer, including lung adenocarcinoma, by administering a kinase inhibitor alone or in combination with another therapeutic agent or modality.
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