Use of modulators of ccr5 in the treatment of cancer and cancer metastasis

Abstract

This disclosure is directed, in part, to a method of determining whether a subject having cancer is at risk for developing metastasis of the cancer. In one embodiment, the method comprises (a) obtaining a biological sample from the subject having cancer; (b) determining CCR5 expression level and/or expression level of at least one of CCR5 ligands in the biological sample; and (c) if the expression level of CCR5 and/or of at least one of CCR5 ligands determined in step (b) is increased compared to CCR5 expression level and/or expression level of at least one of CCR5 ligands in a control sample, then the subject is identified as likely at risk for developing metastasis of the cancer.

1 .- 23 . (canceled) 
     
     
         24 . A method of inhibiting breast cancer cell extravasation of a non-metastatic breast cancer cell in a subject having breast cancer, the method comprising:
 administering to the subject a therapeutically effective amount of a CCR5 antagonist to inhibit breast cancer cell extravasation of the non-metastatic breast cancer cell in the subject.   
     
     
         25 . The method of  claim 24 , wherein the CCR5 antagonist is 4-difluoro-N-[(1S)-3-[(1R,5S)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8- azabicyclo[-3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide. 
     
     
         26 . The method of  claim 24 , wherein the CCR5 antagonist is (4,6-dimethylpyrimidin-5-yl)-[4-[(3S)-4-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-3-methylpiperazin-1-yl]-4-methylbiberidin-1-yl]4-methanone. 
     
     
         27 . The method of  claim 24 , wherein the at least one metastatic site is located in one or more organs of the subject. 
     
     
         28 . The method of  claim 27 , wherein the one or more organs is selected from liver, brain, bladder, lung, adrenal gland, kidney, bone, or combinations thereof. 
     
     
         29 . The method of  claim 24 , wherein the method further comprises determining that the subject has an increased level of expression of CCR5 and/or at least one of CCR5 ligands in a biological sample obtained from the subject as compared to a normal level of expression of CCR5 and/or at least one of CCR5 ligands in a normal control breast tissue sample prior to administering to the subject the therapeutically effective amount of the CCR5 antagonist to inhibit breast cancer cell extravasation in the subject.