Methods of treating urothelial carcinoma
AssigneeFoundation Medicine, Inc.
InventorsSiraj Mahamed Ali, Matthew J. Hawryluk, Jeffrey S. Ross, Philip James Stephens
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Abstract
Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.
Claims21
-30. (canceled)
A method of treating a subject having a urothelial carcinoma, comprising administering to the subject an effective amount of an agent that targets and/or inhibits HER2, thereby treating the urothelial carcinoma.
A method of treating a subject having a carcinoma, comprising:
- acquiring knowledge of:
- (a) the presence of an alteration in HER2;
- and
- (b) the presence of a micropapillary histology in the subject, or a cancer or tumor sample from the subject;
- and
- administering to the subject an effective amount of an agent that targets and/or inhibits HER2, wherein the carcinoma is chosen from a cancer of the urinary tract, bladder, or urothelial cells,
- thereby treating the carcinoma.
A method of determining the presence of a HER2 alteration in a urothelial and/or a micropapillary carcinoma, comprising (i), (ii) or both (i)-(ii):
- (i) acquiring knowledge that a nucleic acid molecule comprising the HER2 alteration is present in a tumor sample from a subject;
- and/or
- (ii) acquiring knowledge of a micropapillary histology in a tumor sample from a subject;
- and
- responsive to a determination of the presence of the HER2 alteration and/or micropapillary histology, the method further comprises one or more of:
- (1) stratifying a patient population;
- (2) identifying or selecting the subject as likely or unlikely to respond to a HER2 inhibitor treatment;
- (3) selecting a treatment option comprising an agent that targets and/or inhibits HER2;
- (4) administering an agent that targets and/or inhibits HER2;
- or
- (5) evaluating the likelihood of increased or decreased patient survival.
A method for screening for an agent that inhibits the expression or activity of HER2 having an alteration, comprising:
- optionally, determining if the alteration is present;
- contacting a polypeptide or protein comprising the alteration or a host cell expressing the alteration with a candidate agent;
- and
- detecting a change in a parameter associated with the alteration,
- wherein said parameter is selected from one or more of:
- (i) direct binding of the candidate agent to the polypeptide or protein comprising the alteration;
- (ii) a change in kinase activity;
- (iii) a change in an activity of a cell containing the alteration;
- (iv) a change in tumor present in an animal subject;
- or
- (v) a change in the level of the polypeptide or protein comprising the alteration or a nucleic acid molecule comprising the alteration.
A kit comprising an agent that targets and/or inhibits HER2, or a composition comprising an agent that targets and/or inhibits HER2, with instructions for use in treating a urothelial and/or a micropapillary urothelial carcinoma, and/or instructions for determining the presence of a HER2 alteration and/or a MPUC histology, wherein the HER2 alteration is chosen from:
- (i) a substitution, a deletion or an insertion;
- (ii) an alteration in the extracellular domain of HER2;
- (iii) an alteration in domain II of HER2;
- (iv) a missense mutation;
- (v) a substitution at position 310 of HER2;
- (vi) a substitution of a serine residue at position 310 of HER2 to phenylalanine or tyrosine;
- (vii) a substitution at position 157 of HER2;
- or
- (viii) a substitution of an arginine residue at position 157 of HER2 to tryptophan.
A purified or an isolated preparation of a nucleic acid derived from a urothelial and/or a micropapillary urothelial carcinoma, containing an interrogation position useful for determining if a HER2 alteration is present, disposed in a sequencing device, or a sample holder for use in such a device, wherein the HER2 alteration is chosen from:
- (i) a substitution, a deletion or an insertion;
- (ii) an alteration in the extracellular domain of HER2;
- (iii) an alteration in domain II of HER2;
- (iv) a missense mutation;
- (v) a substitution at position 310 of HER2;
- (vi) a substitution of a serine residue at position 310 of HER2 to phenylalanine or tyrosine;
- (vii) a substitution at position 157 of HER2;
- or
- (viii) a substitution of an arginine residue at position 157 of HER2 to tryptophan.
A reaction mixture, comprising:
- a detection reagent, or a purified or isolated preparation thereof;
- and
- a target nucleic acid derived from a urothelial and/or a micropapillary urothelial carcinoma cell, which comprises a sequence having an interrogation position for a HER2 alteration, wherein the HER2 alteration is chosen from:
- (i) a substitution, a deletion or an insertion;
- (ii) an alteration in the extracellular domain of HER2;
- (iii) an alteration in domain II of HER2;
- (iv) a missense mutation;
- (v) a substitution at position 310 of HER2;
- (vi) a substitution of a serine residue at position 310 of HER2 to phenylalanine or tyrosine;
- (vii) a substitution at position 157 of HER2;
- or
- (viii) a substitution of an arginine residue at position 157 of HER2 to tryptophan.
Dependencies are inferred from the claim text.