Novel chemical entities affecting neuroblastoma tumor-initiating cells

Abstract

Disclosed are neuroblastoma tumor-initiating cell inhibiting compositions comprising chemical entities capable of affecting neuroblastoma tumor-initiating cells. Pharmaceutical preparations that include these chemical entities are also provided for the treatment of neuroblastoma. These pharmaceutical preparations are suitable for the treatment of humans, and are particularly suited for the treatment of children of 12 years of age or younger having neuroblastoma. The compositions and pharmaceutical preparations posses reduced normal cell cytotoxicity. The compositions and pharmaceutical preparations may be used alone or together with other conventional neuroblastoma preparations as part of a clinical regimen in the treatment and management of neuroblastoma.

1 - 7 . (canceled) 
   
   
       8 . A method comprising the following steps:
 (a) providing neuroblastoma tumor-initiating cells; and   (b) administering an effective amount of a composition comprising a chemical entity that selectively targets neuroblastoma tumor-initiating cells to said neuroblastoma tumor-initiating cells.   
   
   
       9 . The method of  claim 8  wherein said chemical entity is selected from the following:
 10-Hydroxycamtothecin;   2,3-Dimethoxy-1,4-naphthoquinone;   4′-Demethylepipodophyllotoxin;   Amsacrine Hydrochloride;   Andrographolide;   Antimycin A;   Azaguanine-8;   Benzalkonium chloride;   Benzethonium chloride;   Bepridil hydrochloride;   beta-peltatin;   Camptothecine (S.+);   Cetylpyridinium chloride;   Chelerythrine chloride;   Cholestan-3beta.5alpha.6beta-Triol;   Ciclopirox Ethanolamine;   Ciclopirox Olamine;   Clofazimine;   Convallatoxin;   Crassin Acetate;   Crinamine;   Cycloheximide;   Cytosine-1-beta-D-arabinofuranoside hydrochloride;   Dequalinium analog. C-14 linker;   Dequalinium dichloride;   Digoxigenin;   DL-Stearoylcarnitine chloride;   Erysolin;   Gambogic acid;   Imidaclopride;   Limonin;   Loratadine;   Mechlorethamine;   Meclizine hydrochloride;   MG 624;   Mycophenolic acid;   Oxybendazole;   Paclitaxel;   Pararosaniline pamoate;   Parthenolide;   Podophyllotoxin;   Primaquine diphosphate;   Scoulerine;   Taxol;   Teniposide; or   Vinblastine sulfate   
   
   
       10 . (canceled) 
   
   
       11 . The method of  claim 8  wherein the composition further comprises ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, or vincristine sulfate. 
   
   
       12 . The method of  claim 8  wherein the neuroblastoma tumor-initiating cells are derived from an animal having neuroblastoma. 
   
   
       13 . The method of  claim 8  wherein the composition has a reduced non-neuroblastoma tumor-initiating cell cytotoxicity. 
   
   
       14 . The method of  claim 8  wherein the composition is essentially free of non-neuroblastoma tumor cell inhibiting activity. 
   
   
       15 . A method comprising the following steps:
 (a) identifying an animal having neuroblastoma; and   (b) administering to said animal a composition comprising an effective amount of a chemical entity that selectively targets neuroblastoma tumor-initiating cells.   
   
   
       16 . The method of  claim 15  wherein said chemical entity is selected from the following:
 10-Hydroxycamtothecin;   2,3-Dimethoxy-1,4-naphthoquinone;   4′-Demethylepipodophyllotoxin;   Amsacrine Hydrochloride;   Andrographolide;   Antimycin A;   Azaguanine-8;   Benzalkonium chloride;   Benzethonium chloride;   Bepridil hydrochloride;   beta-peltatin;   Camptothecine (S.+);   Cetylpyridinium chloride;   Chelerythrine chloride;   Cholestan-3beta.5alpha.6beta-Triol;   Ciclopirox Ethanolamine;   Ciclopirox Olamine;   Clofazimine;   Convallatoxin;   Crassin Acetate;   Crinamine;   Cycloheximide;   Cytosine-1-beta-D-arabinofuranoside hydrochloride;   Dequalinium analog. C-14 linker;   Dequalinium dichloride;   Digoxigenin;   DL-Stearoylcarnitine chloride;   Erysolin;   Gambogic acid;   Imidaclopride;   Limonin;   Loratadine;   Mechlorethamine;   Meclizine hydrochloride;   MG 624;   Mycophenolic acid;   Oxybendazole;   Paclitaxel;   Pararosaniline pamoate;   Parthenolide;   Podophyllotoxin;   Primaquine diphosphate;   Scoulerine;   Taxol;   Teniposide; or   Vinblastine sulfate   
   
   
       17 . The method of  claim 15  wherein the composition further comprises ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, or vincristine sulfate. 
   
   
       18 . The method of  claim 15  wherein the animal is a human of 12 years of age or younger. 
   
   
       19 . The method of  claim 15  wherein the composition is essentially free of non-neuroblastoma tumor-initiating cell inhibiting activity. 
   
   
       20 . (canceled)