Methods of treating cholangiocarcinoma
Inventors
Ali, Siraj Mahamed • Hawryluk, Matthew J. • He, Jie • Lipson, Doron • Miller, Vincent A. • Ross, Jeffrey S. • Stephens, Philip James
Assignees
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Publication Number
US-11771698-B2
Publication Date
2023-10-03
Expiration Date
Abstract
Methods and compositions for treating cholangiocarcinoma.
Core Innovation
A method of treating a subject having a cholangiocarcinoma includes administering an effective amount of a therapeutic agent that antagonizes or inhibits a fibroblast growth factor receptor 2 (FGFR2) gene or gene product, or a neurotrophic tyrosine receptor kinase, type 1 (NTRK1) gene or gene product, thereby treating the cholangiocarcinoma in the subject. The approach is directed to antagonizing or inhibiting FGFR2 and/or NTRK1 gene or gene product activity in the context of cholangiocarcinoma.
The method further includes acquiring knowledge of whether a sample from the subject contains a fusion polypeptide or a fusion nucleic acid molecule encoding the fusion polypeptide. The fusion polypeptide is one of several specified FGFR2 fusion polypeptides defined by particular exon fusion junctions or includes a RABGAP1L-NTRK1 fusion polypeptide. Determining fusion presence supports treatment relevance to specified fusion molecules.
The method includes determining the presence of the fusion polypeptide or the fusion nucleic acid molecule encoding the fusion polypeptide by sequencing. The fusion-based knowledge acquisition is integrated with the treatment, linking the administration of an FGFR2- or NTRK1-directed therapeutic agent to the presence of specified fusion alterations in the subject’s sample. The disclosed fusion targets include FGFR2-TACC3, FGFR2-KIAA1598, BICC1-FGFR2, PARK2-FGFR2, FGFR2-NOL4, ZDHHC6-FGFR2, and RABGAP1L-NTRK1.
The treatment method is applicable to cholangiocarcinoma categorized as specific intrahepatic or extrahepatic cancer stages, including enumerated stage categories. This provides explicit stage applicability for the cholangiocarcinoma populations described for receiving the FGFR2- or NTRK1-directed therapeutic agent. The document also references therapeutic agent classes and reagent types associated with FGFR2/NTRK1 fusion-alteration detection and treatment in cholangiocarcinoma.
Claims Coverage
The independent claim is directed to treating cholangiocarcinoma by administering an FGFR2- or NTRK1-inhibiting therapeutic agent. Additional dependents extend coverage by specifying main inventive features such as fusion-alteration knowledge acquisition using sequencing, narrowing the fusion targets, and restricting applicability by intrahepatic/extrahepatic stage categories.
Administering an effective FGFR2 or NTRK1 antagonizing or inhibiting therapeutic agent
Administering to the subject an effective amount of a therapeutic agent that antagonizes or inhibits a fibroblast growth factor receptor 2 (FGFR2) gene or gene product, or a neurotrophic tyrosine receptor kinase, type 1 (NTRK1) gene or gene product, thereby treating the cholangiocarcinoma in the subject.
Acquiring fusion-alteration knowledge of fusion polypeptide or fusion nucleic acid encoding the fusion polypeptide
Acquiring knowledge of whether a sample from the subject contains a fusion polypeptide or a fusion nucleic acid molecule encoding that fusion polypeptide, where the fusion polypeptide is one of several specified FGFR2 fusion polypeptides defined by particular exon fusion junctions or a RABGAP1L-NTRK1 fusion polypeptide.
Sequencing to determine presence of the fusion polypeptide or fusion nucleic acid
Determining the presence of the fusion polypeptide or the fusion nucleic acid molecule encoding the fusion polypeptide comprises sequencing.
Treating cholangiocarcinoma within enumerated intrahepatic or extrahepatic stage categories
Applying the method to cholangiocarcinoma categorized as specific intrahepatic or extrahepatic cancer stages, including enumerated stage groupings.
Across the independent claim and the identified inventive dependents, coverage centers on administering an FGFR2- or NTRK1-targeting therapeutic agent for cholangiocarcinoma, with optional fusion-based patient stratification that acquires knowledge of specified fusion polypeptides/nucleic acids and determines their presence by sequencing, and with explicit applicability to enumerated intrahepatic/extrahepatic stage categories.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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