INHIBITORS OF ATYPICAL PROTEIN KINASE C AND THEIR USE IN TREATING HEDGEHOG PATHWAY-DEPENDENT CANCERS
Methods for treating hedgehog pathway-dependent cancers are provided. Aspects of the methods include the inhibition of hedgehog pathway-dependent cancer growth, proliferation, or metastasis that is promoted by hedgehog pathway signaling. In particular, methods of treating hedgehog pathway-dependent cancers with inhibitors of atypical protein kinase C iota are disclosed.
1 . A method of treating a subject for a hedgehog pathway-dependent cancer, the method comprising administering to the subject a therapeutically effective amount of a composition comprising:
or a pharmaceutically acceptable salt thereof.
2 . The method according to claim 1 , wherein the cancer is basal cell carcinoma (BCC).
3 . The method of claim 1 , wherein the cancer comprises a constitutively active hedgehog pathway.
4 . The method of claim 1 , wherein the cancer is metastatic.
5 . The method of claim 1 , wherein multiple cycles of treatment are administered to the subject for a time period sufficient to effect at least a partial tumor response.
6 . The method of claim 5 , wherein the time period is at least 6 months.
7 - 10 . (canceled)
11 . The method of claim 1 , further comprising administering to the subject an additional anti-cancer therapy selected from surgery, chemotherapy, radiation therapy, immunotherapy, biologic therapy, or a combination thereof.
12 . (canceled)
13 . The method of claim 1 , further comprising administering to the subject a histone deacetylase (HDAC) inhibitor in combination with the composition.
14 . The method of claim 13 , wherein the HDAC inhibitor is vorinostat.
15 . (canceled)
16 . The method of claim 15 , wherein the subject is human.
17 . The method of claim 1 , wherein the composition is administered in an amount sufficient to reduce viability of hedgehog pathway-dependent cancerous cells in the subject.
18 . The method of claim 1 , wherein the composition is administered in an amount sufficient to reduce production of Gli 1 mRNA in hedgehog pathway-dependent cancerous cells in the subject.
19 . The method of claim 1 , wherein the composition is administered in an amount sufficient to reduce growth and cell proliferation of hedgehog pathway-dependent cancerous cells in the subject.
20 . A method of inhibiting growth or proliferation of a hedgehog pathway-dependent cancerous cell, the method comprising contacting the hedgehog pathway-dependent cancerous cell with an effective amount of:
or a pharmaceutically acceptable salt thereof.
21 . The method according to claim 20 , wherein the hedgehog pathway-dependent cancerous cell is a basal cell carcinoma (BCC) cell.
22 . The method of claim 20 , wherein the hedgehog pathway-dependent cancerous cell comprises a constitutively active hedgehog pathway.
23 . The method of claim 20 , wherein the hedgehog pathway-dependent cancerous cell is in vivo or in vitro.
24 . The method of claim 20 , wherein the hedgehog pathway-dependent cancerous cell is a human cancerous cell.
25 . The method of claim 20 , further comprising contacting the hedgehog pathway-dependent cancerous cell with a deacetylase (HDAC) inhibitor.
26 . The method of claim 25 , wherein the HDAC inhibitor is vorinostat.
27 - 30 . (canceled)