Methods for identifying and using inhibitors of casein kinase 1 epsilon isoform for inhibiting the growth and/or proliferation of MYC-driven tumor cells

Patent metadata

Field	Value
Publication number	US-9801853-B2
Application number	US-201113639258-A
Country	US
Kind code	B2
Filing date	Apr 6, 2011
Priority date	Apr 6, 2010
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

In one aspect, the invention provides a method for inhibiting the growth and/or proliferation of a myc-driven tumor cell comprising the step of contacting the tumor cells with a CSNK1ε inhibitor. In another aspect, the invention provides a method of treating a subject suffering from a tumor comprising myc-driven tumor cells, comprising administering to the subject an amount of a composition comprising a CSNK1ε inhibitor effective to inhibit the growth and/or proliferation of the tumor cells.

First claim

The invention claimed is:

1. A method for inhibiting the growth and/or proliferation of a cisplatin resistant ovarian tumor cell having an amplified c-myc gene, comprising the step of contacting the cisplatin resistant ovarian tumor cell having the amplified c-myc gene with a casein kinase 1 epsilon (CSNK1ε) inhibitor.

2. The method of claim 1 , wherein the tumor cell is contacted in vitro.

3. The method of claim 1 , wherein the tumor cell is contacted in vivo in a mammalian subject.

4. The method of claim 1 , wherein the CSNK1ε inhibitor is a small molecule inhibitor.

5. The method of claim 4 , wherein the CSNK1ε inhibitor is selected from the group consisting of IC261, PF-4800567, and PF-670462.

6. A method of treating a subject suffering from a cisplatin resistant ovarian tumor comprising cisplatin resistant ovarian tumor cells having an amplified c-myc gene, comprising administering to the subject an amount of a composition comprising a casein kinase 1 epsilon (CSNK1ε) inhibitor effective to inhibit the growth and/or proliferation of the cisplatin resistant ovarian tumor cells having the amplified c-myc gene.

7. The method of claim 6 , wherein the subject is further provided one or more additional anti-cancer therapies.

8. The method of claim 7 , wherein the additional anti-cancer therapy comprises cisplatin.

9. The method of claim 6 , wherein the CSNK1ε inhibitor is a small molecule inhibitor.

10. The method of claim 9 , wherein the CSNK1ε inhibitor is selected from the group consisting of IC261, PF-4800567, and PF-670462.

11. The method of claim 6 , further comprising the step of determining whether the tumor comprises tumor cells having an amplified c-myc gene prior to administering to said subject suffering from a tumor comprising tumor cells having the amplified c-myc gene said composition comprising a CSNK1e inhibitor.

12. A method of treating cisplatin resistance in ovarian tumor cells comprising the steps of: (i) determining whether said tumor cells overexpress c-Myc and (ii) subsequently administering an effective amount of a casein kinase 1 epsilon (CSNK1ε) inhibitor to said cisplatin resistant ovarian tumor cells.

13. The method of claim 12 , wherein the CSNK1ε inhibitor is a small molecule inhibitor.

14. The method of claim 13 , wherein the small molecule inhibitor is IC261.

15. The method of claim 12 , wherein the subject is further provided one or more additional anti-cancer therapies.

16. The method of claim 15 , wherein the additional anti-cancer therapy comprises cisplatin.

17. A method of treating cisplatin resistance in ovarian tumor cells comprising the steps of: (i) determining whether said tumor cells have an amplified c-myc gene and (ii) subsequently administering an effective amount of a casein kinase 1 epsilon (CSNK1ε) inhibitor to said cisplatin resistant ovarian tumor cells.

18. The method of claim 17 , wherein the CSNK1ε inhibitor is a small molecule inhibitor.

19. The method of claim 18 , wherein the small molecule inhibitor is IC261.

20. The method of claim 17 , wherein the subject is further provided one or more additional anti-cancer therapies.

21. The method of claim 20 , wherein the additional anti-cancer therapy comprises cisplatin.

Assignees

• Grandori Carla
• Toyoshima Masafumi
• Hutchinson Fred Cancer Res

Inventors

• Grandori Carla
• Toyoshima Masafumi

Classifications

• A61K31/404 Primary

  Indoles, e.g. pindolol · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K33/24

  Heavy metals; Compounds thereof · CPC title

• A61K33/243

  Platinum; Compounds thereof · CPC title