Diagnosis and treatment of cancer
The present invention relates to compositions and methods for cancer therapy, including but not limited to, therapies that utilize cancer biomarkers. In particular, the present invention relates to compositions and methods for the prediction of a subject's response to cancer therapies.
1 . Method of treating cancer in a subject:
comprising administering an effective amount of an antigen binding protein to the subject,
wherein the subject has been diagnosed as eligible for treatment with the antigen binding protein targeting a surface antigen expressed on the cancer cells when the measured expression level of Ras associated binding (RAB) protein 5 (RAB5), in the subject's cancer cell sample is decreased as compared to a dichotomizing threshold;
wherein the expression level of RAB5 in cancer cells in a cell sample obtained from the subject has been measured, wherein said measuring has been performed by an in vitro assay, and the expression level has been compared to the dichotomizing threshold;
wherein the antigen binding protein is an antigen-binding protein that does not comprise a drug or toxin, wherein the antigen binding protein is an antibody, or an antigen-binding fragment thereof, that binds to the cell surface antigen;
wherein the surface antigen is a surface antigen internalized by a pathway for endocytosis, wherein said pathway comprises RAB5; and
wherein the surface antigen is selected from the group consisting of human epidermal growth factor receptor (HER)1, HER2, HER3, cluster of differentiation (CD)3, CD19, CD22, CD25 (IL-2Rα), CD30, CD33, CD74, CD79, CEA (CEACAM5 (Carcinoembryonic Antigen Related Cell Adhesion Molecule 5)), FRα (Folate Receptor alpha), epithelial cellular adhesion molecule (EpCAM) (CD326) and Mesothelin (MSLN).
2 . The method of claim 1 , wherein the expression level of RAB5 in the cancer cells has been measured by measuring the level of RAB5 mRNA or RAB5 protein.
3 . The method of claim 1 , wherein the RAB5 is RAB5A, RAB5B or RAB5C.
4 . The method of claim 1 , further comprising measuring the expression level of one or more of RAB4, RAB11 or heat shock protein (HSP)90 in the cancer cells in the cell sample obtained from the subject and optionally, wherein the expression level of one or more of RAB4, RAB11 or HSP90 has been incorporated into an expression index with the RAB5 expression level and the subject has been diagnosed as eligible for treatment with the antigen binding protein when the expression index is decreased as compared to the dichotomizing threshold.
5 . The method of claim 1 , wherein the cancer cells are cancer cells that have been obtained from a surgical tumor sample, a biopsy sample or a blood sample.
6 . The method of claim 1 , wherein the cancer cells are selected from the group consisting of breast cancer cells, colorectal cancer cells, lung cancer cells, prostate cancer cells, melanoma cells, glioblastoma cells, pancreatic cancer cells, renal cell carcinoma cells, ovarian cancer cells, bladder cancer cells, endometrial cancer cells, gastrointestinal cancer cells, mesothelioma cells, multiple myeloma cells, acute myelogenous leukemia cells, acute lymphoblastic leukemia cells, and Non-Hodgkin's Lymphoma.
7 . The method of claim 1 , wherein the expression of the surface antigen on the cancer cells of the cell sample obtained from the subject has been assayed.
8 . The method of claim 1 , wherein the cancer cells are breast cancer cells.
9 . The method of claim 8 , wherein the surface antigen is selected from the group consisting of HER1, HER2, HER3, and the antibody binding protein is targeting said surface antigen.
10 . The method of claim 9 , wherein the surface antigen is HER2.
11 . The method of claim 1 , wherein the antigen binding protein is selected from trastuzumab, pertuzumab and cetuximab.
12 . The method of claim 1 , wherein the antigen binding protein is trastuzumab.