Inhibitors of ephrin b1 for tumor treatment

Abstract

Disclosed herein are compositions and methods for tumor treatment involving administering to a subject having a tumor with an amount effective to limit tumor growth or metastasis of an ephrin B1 inhibitor, or a pharmaceutically acceptable salt thereof; and/or an inhibitor of tumor exosomal release, or a pharmaceutically acceptable salt thereof

1 . A method for tumor treatment comprising administering to a subject having a tumor with an amount effective to limit tumor growth or metastasis of:
 (a) an ephrin B1 inhibitor, or a pharmaceutically acceptable salt thereof; and/or   (b) an inhibitor of tumor exosomal release, or a pharmaceutically acceptable salt thereof.   
     
     
         2 . The method of  claim 1 , wherein the method limits tumor innervation. 
     
     
         3 . The method of  claim 1 , wherein the method comprises administering to the subject an amount effective of an ephrin B1 inhibitor, wherein the ephrin B1 inhibitor is selected from the group consisting ephrin B1-specific antibodies, aptamers, small interfering RNAs, small internally segmented interfering RNAs, short hairpin RNAs, microRNAs, and/or antisense oligonucleotides. 
     
     
         4 . The method of  claim 3 , wherein the ephrin B1 inhibitor comprises ephrin B1-specific antibodies. 
     
     
         5 . The method of  claim 4 , wherein the ephrin B1-specific antibodies bind to one or more epitopes in the extracellular domain of ephrin B1. 
     
     
         6 . The method of  claim 1 , wherein the method comprises administering to the subject an amount effective of an inhibitor of tumor exosomal release. 
     
     
         7 . The method of  claim 6 , wherein the inhibitor of tumor exosomal release comprises an inhibitor of Rab27a and/or an inhibitor of Rab27b. 
     
     
         8 . The method of  claim 6 , wherein the inhibitor of Rab27a and/or the inhibitor of Rab27b are selected from the group consisting Rab27a and/or Rab27b-specific antibodies, aptamers, small interfering RNAs, small internally segmented interfering RNAs, short hairpin RNAs, microRNAs, and/or antisense oligonucleotides. 
     
     
         9 . The method of  claim 1 , wherein the method further comprises administering to the subject an inhibitor of the interaction between E6 and PTPN13, or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the method further comprises administering to the subject an inhibitor of ephrin B1 phosphorylation, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the tumor is an innervated solid tumor. 
     
     
         12 . The method of  claim 1 , wherein the tumor is selected from the group consisting of head, neck, breast, lung, liver, ovarian, colon, colorectal, brain, melanoma, pancreatic, bone, or prostate tumors. 
     
     
         13 . The method of  claim 1 , wherein the tumor is a high-risk human papillomavirus (HPV)-positive tumor. 
     
     
         14 . The method of  claim 13  where the HPV-positive tumor is a tumor of the head or neck. 
     
     
         15 . The method of  claim 14 , wherein the human papillomavirus-positive tumor of the head or neck comprises a squamous cell carcinoma. 
     
     
         16 . The method of  claim 1 , wherein the administering comprises local delivery to the tumor. 
     
     
         17 . The method of  claim 1 , wherein the tumor has a low level of PTPN13 expression, protein level, or protein activity level compared to control. 
     
     
         18 . A method for identifying compounds to treat a tumor, comprising:
 (a) contacting a first population of tumor cells with one or more test compounds; and either   (b) (i) comparing activity of exosomes released from the first population of tumor cells in promoting neurite outgrowth to activity of exosomes released from a control population of tumor cells in promoting neurite outgrowth; wherein test compounds that reduce exosomal-promoted neurite outgrowth compared to the control are candidate compounds for treating a tumor, or (ii) comparing exosomal release from the first population of cells to exosomal release from a control population of tumor cells, wherein test compounds that reduce exosomal release compared to the control are candidate compounds for treating a tumor.   
     
     
         19 .- 21 . (canceled) 
     
     
         22 . A composition comprising:
 (a) an ephrin B1 inhibitor, or a pharmaceutically acceptable salt thereof; and   (b) an inhibitor of Rab27a and/or an inhibitor of Rab27b, or a pharmaceutically acceptable salt thereof.   
     
     
         23 . The composition of  claim 22 , wherein the ephrin B1 inhibitor is selected from the group consisting ephrin B1-specific antibodies, aptamers, small interfering RNAs, small internally segmented interfering RNAs, short hairpin RNAs, microRNAs, and/or antisense oligonucleotides. 
     
     
         24 . The composition of  claim 23 , wherein the ephrin B1 inhibitor comprises ephrin B1-specific antibodies. 
     
     
         25 . (canceled) 
     
     
         26 . The composition of  claim 22 , wherein the inhibitor of Rab27a and/or the inhibitor of Rab27b are selected from the group consisting Rab27a and/or Rab27b-specific antibodies, aptamers, small interfering RNAs, small internally segmented interfering RNAs, short hairpin RNAs, microRNAs, and/or antisense oligonucleotides. 
     
     
         27 .- 30 . (canceled)