Methods of treating fibroblast growth factor 19-mediated cancers and tumors

Abstract

Provided are methods of treating a FGF19-mediated cancer or tumor in a subject by administering to the subject an anti-IL-6 antibody or an anti-IL-6 receptor antibody or an inhibitor of STAT3/JAK signaling pathway, and pharmaceutical compositions relating thereto.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating or preventing a fibroblast growth factor 19 (FGF19)-mediated cancer or tumor in a subject in need thereof, comprising, administering to the subject a therapeutically effective amount of an anti-IL-6 receptor antibody. 
     
     
         46 . The method of  claim 45 , wherein the anti-IL-6 receptor antibody is tocilizumab or sarilumab. 
     
     
         47 . The method of  claim 45 , wherein the anti-IL-6 receptor antibody is tocilizumab, and wherein the dose of the tocilizumab (i) is in the range of about 0.1 to 100 mg/kg per day; (ii) is in the range of about 4 to about 30 mg/kg/day; (iii) is about 4 mg/kg per day; (iv) is about 8 mg/kg per day; (v) is about 10 mg/kg per day; or (vi) is about 12 mg/kg per day. 
     
     
         48 . The method of  claim 45 , wherein the anti-IL-6 receptor antibody is tocilizumab, and wherein the tocilizumab is administered once every 3 or 4 weeks by intravenous infusion. 
     
     
         49 . The method of  claim 45 , wherein the administration treats the cancer or tumor without substantially affecting the metabolic function mediated by FGF19. 
     
     
         50 . The method of  claim 49 , wherein the metabolic function is the ability to regulate bile acid synthesis, glucose metabolism or energy homeostasis. 
     
     
         51 . The method of  claim 45 , wherein the FGF19-mediated cancer or tumor is a liver, lung, breast, colon, or esophageal cancer or tumor. 
     
     
         52 . The method of  claim 45 , wherein the FGF19-mediated cancer or tumor is a hepatocellular carcinoma (HCC). 
     
     
         53 . The method of  claim 45 , wherein the expression level of FGF19 or at least one STAT3 target gene is amplified in the cancer or tumor as compared to a control. 
     
     
         54 . The method of  claim 53 , wherein the at least one STAT3 target gene is BIRC5, BCL2, HSPA4, BCL2L1, or MCL1. 
     
     
         55 . The method of  claim 53 , wherein the expression level of the FGF19 or the at least one STAT target gene is determined by Quantitative Polymerase Chain Reaction (qPCR), Real-Time Polymerase Chain Reaction (RT-PCR), RNA-seq, Microarray, Serial Analysis of Gene Expression (SAGE), MassARRAY technique, or Fluorescence In Situ Hybridization (FISH), an immunohistochemistry (IHC) assay, an immunoblotting (IB) assay, flow cytometry (FACS), or Enzyme-Linked Immunosorbent Assay (ELISA). 
     
     
         56 . A method of modulating FGF19 signaling in a liver cell, comprising contacting the cell with an anti-IL-6 receptor antibody.