Inhibition of leukotriene synthesis and activity in the treatment of sonic hedgehog-associated medulloblastoma
Treating Sonic Hedgehog-Associated Medulloblastoma comprises inhibiting the synthesis or biologic activity of leukotrienes that drive Nestin expression in cancerous or precancerous granule neuron precursors and that further drive growth and proliferation of medulloblastoma cells through Nestin-mediated aberrant Sonic Hedgehog signaling.
1. A method for treating Sonic Hedgehog-Associated Medulloblastoma, comprising administering to a subject in need thereof (a) an agent that inhibits the biologic activity of 5-lipoxygenase in an amount effective to inhibit the biologic activity of 5-lipoxygenanse in sonic hedgehog-associated medulloblastoma cells in the subject, (b) an agent that inhibits the biologic activity of the 5-lipoxygenase activating protein in an amount effective to inhibit the biologic activity of the 5-lipoxygenase activating protein in sonic hedgehog-associated medulloblastoma cells in the subject, or (c) an agent that blocks the interaction of a leukotriene with the leukotriene receptor CysLT1 or CysLT2 in an amount effective to block the interaction of a leukotriene with the leukotriene receptor CysLT1 or CysLT2 in sonic hedgehog-associated medulloblastoma cells in the subject, such that Sonic Hedgehog-Associated Medulloblastoma is treated in the subject.
2. The method of claim 1 , wherein the sonic hedgehog-associated medulloblastoma cells express Nestin.
3. The method of claim 1 , wherein inhibiting the biologic activity of 5-lipoxygenase in the sonic hedgehog-associated medulloblastoma cells inhibits proliferation or growth of the sonic hedgehog-associated medulloblastoma cells.
4. The method of claim 1 , wherein inhibiting the biologic activity of the 5-lipoxygenase activating protein in the sonic hedgehog-associated medulloblastoma cells inhibits proliferation or growth of the sonic hedgehog-associated medulloblastoma cells.
5. The method of claim 1 , wherein blocking the interaction of a leukotriene with the leukotriene receptor CysLT1 or CysLT2 in the sonic hedgehog-associated medulloblastoma cells inhibits proliferation or growth of the sonic hedgehog-associated medulloblastoma cells.
6. The method of claim 1 , wherein the agent that specifically inhibits the expression or biologic activity of 5-lipoxygenase comprises Zileuton (Formula III) or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the agent that specifically inhibits the expression or biologic activity of the 5-lipoxygenase activating protein comprises MK886 (Formula I) or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the agent that blocks the interaction of a leukotriene with the leukotriene receptor CysLT1 or CysLT2 comprises Montelukast (Formula II) or Zafirlukast (Formula IV) or a pharmaceutically acceptable salt of Montelukast or Zafirlukast.
9. The method of claim 1 , wherein the subject is a human being.
10. A method for treating Sonic Hedgehog-Associated Medulloblastoma, comprising administering to a subject in need thereof Zileuton (Formula III) or a pharmaceutically acceptable salt thereof in an amount effective to treat Sonic Hedgehog-Associated Medulloblastoma in the subject.
11. The method of claim 10 , wherein the Zileuton (Formula III) or pharmaceutically acceptable salt thereof is administered to the brain of the subject.
12. The method of claim 10 , wherein cells of the sonic hedgehog-associated medulloblastoma express Nestin.
13. The method of claim 10 , wherein the Zileuton (Formula III) or pharmaceutically acceptable salt thereof inhibits proliferation or growth of sonic hedgehog-associated medulloblastoma cells.
14. The method of claim 10 , wherein the subject is a human being.
15. A method for treating Sonic Hedgehog-Associated Medulloblastoma, comprising administering to a subject in need thereof Montelukast (Formula II), Zafirlukast (Formula IV), or a pharmaceutically acceptable salt thereof in an amount effective to treat Sonic Hedgehog-Associated Medulloblastoma in the subject.
16. The method of claim 15 , wherein the Montelukast (Formula II), Zafirlukast (Formula IV), or pharmaceutically acceptable salt thereof is administered to the brain of the subject.
17. The method of claim 15 , wherein cells of the sonic hedgehog-associated medulloblastoma express Nestin.
18. The method of claim 15 , wherein the Montelukast (Formula II), Zafirlukast (Formula IV), or pharmaceutically acceptable salt thereof inhibits proliferation or growth of sonic hedgehog-associated medulloblastoma cells.
19. The method of claim 15 , wherein the method comprises administering to the subject Montelukast (Formula II) or a pharmaceutically acceptable salt thereof in an amount effective to treat Sonic Hedgehog-Associated Medulloblastoma in the subject.
20. The method of claim 15 , wherein the method comprises administering to the subject Zafirlukast (Formula IV) or a pharmaceutically acceptable salt thereof in an amount effective to treat Sonic Hedgehog-Associated Medulloblastoma in the subject.
21. The method of claim 15 , wherein the subject is a human being.
22. A method for treating Sonic Hedgehog-Associated Medulloblastoma, comprising administering to a subject in need thereof MK886 (Formula I) or a pharmaceutically acceptable salt thereof in an amount effective to treat Sonic Hedgehog-Associated Medulloblastoma in the subject.
23. The method of claim 22 , wherein the MK886 (Formula I) or pharmaceutically acceptable salt thereof is administered to the brain of the subject.
24. The method of claim 22 , wherein cells of the sonic hedgehog-associated medulloblastoma express Nestin.
25. The method of claim 22 , wherein the MK886 (Formula I) or pharmaceutically acceptable salt thereof inhibits proliferation or growth of sonic hedgehog-associated medulloblastoma cells.
26. The method of claim 22 , wherein the subject is a human being.