Methods of cancer therapy by inhibiting fusion polypeptides comprising fibroblast growth factor receptor 2 (FGFR2) and vinculin (VCL)
AssigneeDebiopharm International S.A.
InventorsHiroaki Tanaka, Corinne Moulon, Anne Vaslin Chessex, Jérôme Wojcik, Claudia Armenise
Life of this patent
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Abstract
Fusion polypeptides have an FGFR2 polypeptide and cDNAs encode such fusion polypeptides. Methods of diagnosing the presence of the fusion polypeptides or of a gene or RNA sequence coding therefore in a sample from a subject as well as methods of treatment of a tumor instructed by the latter diagnosis.
Claims22
A method of cancer therapy, comprising subjecting a subject containing or expressing a gene for a fusion polypeptide or expressing the fusion polypeptide, to a therapeutic regimen that comprises administration of a pharmaceutical composition comprising (1) an inhibitor of fibroblast growth factor receptor (FGFR) kinase activity, (2) an antibody or antigen-binding fragment that binds the fusion polypeptide, (3) an antisense oligonucleotide capable of hybridization in a live cell to a messenger RNA encoding the fusion polypeptide, which hybridization has the effect of preventing or reducing translation of the messenger RNA or (4) an siRNA directed to a messenger RNA encoding the fusion polypeptide,
- wherein the fusion polypeptide comprises:
- a first polypeptide having 95% or more identity with a wild-type FGFR2 polypeptide or with a fragment thereof;
- and
- a second polypeptide having 95% or more identity with a wild-type vinculin (VCL) polypeptide or with a fragment thereof.
A method of cancer therapy, comprising the steps of
- (a) taking, from a subject suffering from cancer, a biopsy containing cancer cells, or a fluid sample containing cancer cells or circulating tumor DNA;
- (b) determining whether the cancer cells or circulating tumor DNA contains or expresses a gene encoding a fusion polypeptide or expresses the fusion polypeptide;
- (c) selecting the subject containing or expressing the gene for the fusion polypeptide or expressing the fusion polypeptide for the treatment of step d;
- and
- (d) subjecting the selected subject to a therapeutic regimen that comprises administration of a pharmaceutical composition comprising (1) an inhibitor of FGFR kinase activity, (2) an antibody or antigen-binding fragment that binds the fusion polypeptide, (3) an antisense oligonucleotide capable of hybridization in a live cell to a messenger RNA encoding the fusion polypeptide, which hybridization has the effect of preventing or reducing translation of the messenger RNA or (4) a siRNA directed to a messenger RNA encoding the fusion polypeptide,
- wherein the fusion polypeptide comprises:
- a first polypeptide having 95% or more identity with a wild-type FGFR2 polypeptide or with a fragment thereof;
- and
- a second polypeptide having 95% or more identity with a wild-type VCL polypeptide or with a fragment thereof.
A method of cancer therapy, comprising subjecting a subject containing or expressing a gene for a fusion polypeptide or expressing the fusion polypeptide, to a therapeutic regimen that comprises administration of a pharmaceutical composition comprising (1) an inhibitor of FGFR kinase activity, (2) an antibody or antigen-binding fragment that binds the fusion polypeptide, (3) an antisense oligonucleotide capable of hybridization in a live cell to a messenger RNA encoding the fusion polypeptide, which hybridization has the effect of preventing or reducing translation of the messenger RNA or (4) an siRNA directed to a messenger RNA encoding the fusion polypeptide,
- wherein the fusion polypeptide has 95% or more identity with the sequence of SEQ ID NO:
- 3.
A method of cancer therapy, comprising:
- (a) taking, from a subject suffering from cancer, a biopsy containing cancer cells, or a fluid sample containing cancer cells or circulating tumor DNA;
- (b) determining whether the cancer cells or circulating tumor DNA contains or expresses a gene encoding a fusion polypeptide or expresses the fusion polypeptide;
- (c) selecting the subject containing or expressing the gene for the fusion polypeptide or expressing the fusion polypeptide for the treatment of step d;
- and
- (d) subjecting the selected subject to a therapeutic regimen that comprises administration of a pharmaceutical composition comprising (1) an inhibitor of FGFR kinase activity, (2) an antibody or antigen-binding fragment that binds the fusion polypeptide, (3) an antisense oligonucleotide capable of hybridization in a live cell to a messenger RNA encoding the fusion polypeptide, which hybridization has the effect of preventing or reducing translation of the messenger RNA or (4) a siRNA directed to a messenger RNA encoding the fusion polypeptide,
- wherein the fusion polypeptide has 95% or more identity with the sequence of SEQ ID NO:
- 3.
Dependencies are inferred from the claim text.