Compositions and Methods for Treating and/or Preventing Cancer by Inhibiting Fatty Acid Binding Proteins

Abstract

The present invention concerns methods and compositions for the inhibition or reduction of the primary tumor and metastasis by inhibition of fatty acid binding proteins.

1 . A method of inhibiting a primary tumor or cancer cell metastasis comprising administering to a subject having or suspected of having cancer an effective amount of a fatty acid binding protein (FABP) inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the FABP inhibitor is a FABP 4 inhibitor. 
     
     
         3 . The method of  claim 2 , wherein the FABP4 inhibitor is a carbazole butanoic acid, aryl sulfonamide, sulfonylthiophene derivative, 4-hydroxypyrimidine, tetrahydrocarbazole derivative, 2,3-dimethylindole derivative, benzoylbenzene, biphenyl-alkanoic acid derivative, 2-oxazole-alkanoic acid derivative, tetrahydropyrimidone, pyridone, pyrazinone, aryl carboxylic acid, tetrazole, triazolopyrimidinone, and indole derivative. 
     
     
         4 . The method of  claim 3  wherein the FABP4 inhibitor is BMS309403; pyrazole, 4-{[2-(methoxycarbonyl)-5-(2-thienyl)-3-thienyl]amino}-4-oxo-2-butenoic acid; or ((2′-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)(1,1′-biphenyl)-3-yl)oxy)-acetic acid. 
     
     
         5 . The method of  claim 1 , wherein the FABP inhibitor is a FABP5 inhibitor. 
     
     
         6 . The method of  claim 1 , wherein the FABP inhibitor inhibits the activity of more than one FABP. 
     
     
         7 . The method of  claim 1 , wherein the FABP inhibitor is administered intravascularly, intraperitoneally, or orally. 
     
     
         8 . The method of  claim 1 , further comprising administering a second anti-cancer therapy. 
     
     
         9 . The method of  claim 8 , wherein the second anti-cancer therapy is a chemotherapy, radiotherapy, surgery, or immunotherapy. 
     
     
         10 . The method of  claim 9 , wherein the chemotherapy is paclitaxel, cisplatin (CDDP), carboplatin, procarbazine, mechlorethamine, cyclophosphamide, camptothecin, ifosfamide, melphalan, chlorambucil, busulfan, nitrosurea, dactinomycin, daunorubicin, doxorubicin, bleomycin, plicomycin, mitomycin, etoposide (VP16), tamoxifen, raloxifene, estrogen receptor binding agents, paclitaxel, taxotere, gemcitabine, navelbine, a farnesyl-protein transferase inhibitor, a PARP inhibitor, a c-Met inhibitor, an anti-angiogenic, transplatinum, 5-fluorouracil, vincristin, vinblastin, topotecan or methotrexate. 
     
     
         11 . The method of  claim 1 , wherein the FABP inhibitor is administered in a dose of 5 mg/kg/day to 100 mg/kg/day. 
     
     
         12 . The method of  claim 1 , wherein the FABP inhibitor is administered daily. 
     
     
         13 . The method of  claim 1 , wherein the metastasis is a metastasis to the omentum, kidney, liver, breast, peritoneum, bladder, uterus, ovary, fallopian tube, skin, lung, lymph nodes, brain, and/or bone. 
     
     
         14 .- 24 . (canceled) 
     
     
         25 . A method of inhibiting cancer cell growth comprising administering to a cancer patient an effective amount of a fatty acid binding protein (FABP) inhibitor. 
     
     
         26 . The method of  claim 25 , wherein the FABP inhibitor is a FABP4 inhibitor. 
     
     
         27 . The method of  claim 25 , wherein the FABP inhibitor is a FABP5 inhibitor. 
     
     
         28 . The method of  claim 25 , wherein the FABP inhibitor inhibits the activity of more than one FABP. 
     
     
         29 . The method of  claim 25  wherein the cancer cell is an ovarian, breast, gastric, colon, pancreatic, gastrointestinal tract or prostate cancer cell. 
     
     
         30 . A method of increasing cancer cell death comprising administering to a cancer patient an effective amount of a fatty acid binding protein (FABP) inhibitor. 
     
     
         31 .- 36 . (canceled)