Methods for treating hepatocellular carcinoma

Abstract

The present invention provides methods and compositions for treating hepatocellular carcinoma (HCC) by administering a composition comprising nanoparticles that comprise a taxane and an albumin. The invention also provides combination therapy methods of treating HCC comprising administering to an individual an effective amount of a composition comprising nanoparticles that comprise a taxane and an albumin and another agent, such as an agent that inhibits microtubule disassembly.

1 . A method of treating hepatocellular carcinoma (HCC) in an individual in need thereof, comprising administering to the individual an effective amount of a composition comprising nanoparticles comprising a taxane and an albumin. 
     
     
         2 . The method of  claim 1 , further comprising administering to the individual an effective amount of at least one other agent, wherein said other agent inhibits microtubule disassembly. 
     
     
         3 . The method of  claim 2 , wherein the nanoparticle composition and the other agent are administered simultaneously or sequentially. 
     
     
         4 . The method of  claim 2 , wherein the nanoparticle composition and the other agent are administered concurrently. 
     
     
         5 . The method of  claim 2 , wherein the other agent inhibits a molecule that promotes microtubule disassembly directly or indirectly. 
     
     
         6 . The method of  claim 2 , wherein the other agent inhibits a molecule selected from the group consisting of ABP1, ARHGAP4, HSPA8, LCP1, PACSIN2, RUNX1T1, STMN1, and Tubulin, and TUBB4. 
     
     
         7 . The method of  claim 6 , wherein the other agent is an inhibitor of STMN1. 
     
     
         8 . The method of  claim 7 , wherein the other agent is an siRNA against STMN1. 
     
     
         9 . The method of  claim 7 , wherein the other agent is a gamboge or a derivative thereof. 
     
     
         10 . The method of  claim 2 , wherein the other agent activates a molecule that promotes microtubule assembly directly or indirectly. 
     
     
         11 . The method of  claim 2 , wherein the other agent activates a molecule selected from the group consisting of ABI1, BCL2L11, CDC42, CHRM3, CNN3, CSMD1, DDOST, DOCK7, EHMT2, ENAH, ERMAP, ERLF1, HDAC5, LDLRAP1, MCF2, OLA1, RASA1, SHC2, STMN2, and TRIP10. 
     
     
         12 . The method of  claim 1 , wherein the HCC is liver cell carcinoma, fibrolamellar variant of HCC, or mixed hepatocellular cholangiocarcinoma. 
     
     
         13 . The method of  claim 1 , wherein the HCC is early stage HCC, non-metastatic HCC, primary HCC, advanced HCC, locally advanced HCC, metastatic HCC, HCC in remission, recurrent HCC, HCC in an adjuvant setting, or HCC in a neoadjuvant setting. 
     
     
         14 . The method of  claim 1 , wherein the composition comprising nanoparticles comprising a taxane and albumin is administered parenterally. 
     
     
         15 . The method of  claim 14 , wherein the composition comprising nanoparticles comprising a taxane and albumin is administered intravenously, intraarterially, intrahepatically, or intraportally. 
     
     
         16 . The method of  claim 1 , wherein the taxane is paclitaxel. 
     
     
         17 . The method of  claim 1 , wherein the nanoparticles in the composition have an average diameter of no greater than about 200 nm. 
     
     
         18 . The method of  claim 17 , wherein the nanoparticles in the composition have an average diameter of less than about 200 nm. 
     
     
         19 . The method of  claim 1 , wherein the taxane in the nanoparticles are coated with albumin. 
     
     
         20 . The method of  claim 1 , wherein the individual is human. 
     
     
         21 . A kit comprising a) a composition comprising nanoparticles comprising a taxane and an albumin, and b) instruction for administering the nanoparticle composition for treatment of HCC.