Methods for treating cancers comprising k-ras mutations
AssigneeOncoMed Pharmaceuticals, Inc.
InventorsTimothy C. HOEY, Wan-Ching Yen, Marcus M. Fischer
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Abstract
Methods of inhibiting tumor growth, methods of treating cancer, and methods of reducing the frequency of cancer stem cells in a tumor are described. Particularly, the methods are directed to tumors or cancers that comprise a K-ras mutation. The methods described comprise administering a DLL4 antagonist (e.g., an antibody that specifically binds the extracellular domain of human DLL4) to a subject. Related polypeptides and polynucleotides, compositions comprising the DLL4 antagonists, and methods of making the DLL4 antagonists are also described.
Claims18
1-91. (canceled)
A method of treating cancer in a human subject comprising administering a therapeutically effective amount of a delta-like ligand 4 (DLL4) antagonist and at least one additional therapeutic agent to the subject, wherein the cancer is substantially non-responsive to at least one epithelial growth factor receptor (EGFR) inhibitor, and wherein the DLL4 antagonist is an antibody that specifically binds the extracellular domain of human DLL4.
The method of claim 96, wherein the antibody comprises:
- (a) a heavy chain variable region comprising SEQ ID NO:6;
- and
- (b) a light chain variable region comprising SEQ ID NO:10.
The method of claim 104, wherein the chemotherapeutic agent is selected from the group consisting of:
- a topoisomerase inhibitor, an anti-metabolite, an anti-mitotic agent, and an alkylating agent.
A method of selecting a human subject for treatment with a delta-like ligand 4 (DLL4) antagonist, comprising determining if the subject has:
- (a) a cancer comprising a K-ras mutation or
- (b) a cancer that is substantially non-responsive to at least one EGFR inhibitor,
- wherein if the subject has (a) and/or (b), the subject is selected for treatment with a DLL4 antagonist.
Dependencies are inferred from the claim text.