Evaluating mmp expression in patient stratification and other therapeutic, diagnostic and prognostic methods for cancer

Abstract

Provided are compositions, methods and kits for quantifying the expression and/or activity of MMP-14 and other biomarkers of cancer, which may be used diagnostically and prognostically, e.g., in patient stratification and evaluation of appropriate therapeutic regimens.

1 - 2 . (canceled) 
     
     
         3 . A method of monitoring the progress of a therapy for cancer in a subject, the method comprising evaluating an expressional ratio of MMP-14 to MMP-9, an expressional ratio of MMP-14 to MMP-2 or an expressional ratio of MMP-2 to MMP-9 in a sample from the subject, and
 wherein an expressional ratio of MMP-14 to MMP-9 or MMP-2 or an expressional ratio of MMP-2 to MMP-9 is greater than 1 in the subject following treatment compared to a reference set indicates successful progress of the therapy for cancer.   
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 3 , wherein the cancer is selected from the group consisting of: osteotropic cancer, breast cancer, lung cancer, colon cancer and prostate cancer. 
     
     
         6 . The method of  claim 5 , wherein the sample is a tumor biopsy. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 3 , wherein the expressional ratio is the ratio of MMP-14 to MMP-9 expression or the ratio of MMP-14 to MMP-9 protein activity. 
     
     
         9 . The method of  claim 3 , wherein the expressional ratio is the ratio of MMP-14 to MMP-2 expression or the ratio of MMP-14 to MMP-2 protein activity. 
     
     
         10 . The method of  claim 3 , wherein the expression ratio is the ratio of MMP-2 to MMP-9 expression or the ratio of MMP-2 to MMP-9 protein activity. 
     
     
         11 . The method of  claim 3 , wherein the MMP-14 binding protein is an antibody or antibody fragment. 
     
     
         12 . The method of  claim 11 , wherein the antibody fragment is a single chain antibody, a Fab fragment, an sFab fragment, a F(ab′) 2  fragment, an Fd fragment, an Fv fragment, an scFv fragment, or a domain antibody (dAb) fragment. 
     
     
         13 . The method of  claim 11 , wherein the antibody or antibody fragment competes for binding with DX-2400. 
     
     
         14 . The method of  claim 8  or  9 , wherein the expression is protein expression. 
     
     
         15 . The method of  claim 14 , wherein the level of protein expression is determined using an MMP-14, MMP-9 and/or MMP-2 antibody. 
     
     
         16 . The method of  claim 3 , wherein the reference set is determined in the subject before onset of treatment. 
     
     
         17 . The method of  claim 11 , wherein the antibody or antibody fragment is a human antibody, an effectively human antibody or a humanized antibody. 
     
     
         18 . The method of  claim 3 , wherein the cancer is melanoma. 
     
     
         19 . The method of  claim 3 , wherein the cancer is a diffuse large B-cell lymphoma. 
     
     
         20 . The method of  claim 3 , wherein the MMP-14 binding protein comprises heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO:13 and light chain CDR1, CDR2 and CDR3 of SEQ ID NO:14. 
     
     
         21 . The method of  claim 20 , wherein the MMP-14 binding protein is DX-2400. 
     
     
         22 . The method of  claim 20 , wherein the MMP-14 binding protein is M0038-F01. 
     
     
         23 . The method of  claim 3 , wherein the MMP-14 binding protein is DX-2410.