METHODS OF TREATING CANCER HAVING AN ABERRANT EGFR OR KRAS GENOTYPE

• US 20120041070A1
• Filed: 09/30/2011
• Published: 02/16/2012
• Est. Priority Date: 03/31/2009
• Status: Abandoned Application

• Current Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Original Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Inventors: Jin, Shengfang, Su, Shinsan, Van Der Heiden, Matthew
• Application Number:
  US13/249,609
• Publication Number:
  US 20120041070A1
• Time in Patent Office: Days
• US Class Current: 514/635
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention relates to the treating cancer having an aberrant EGFR or KRAS genotype, with an AMPK activator, as well as related methods, compounds and compositions.

Claims

1-13. -13. (canceled)

14. A method of treating a patient suffering from a cancer characterized by cells having an aberrant genotype for EGFR or KRAS, comprising administering to the patient in need thereof a therapeutically effective amount of an AMPK activator.

15. The method of claim 14, wherein the AMPK activator is a direct activator.

18. The method of claim 14, wherein the AMPK activator is administered in conjunction with another anti-cancer agent.

19. The method of claim 14, further comprising the additional step of evaluating the cancer for an aberrant EGFR or KRAS genotype prior to the administration of the AMPK activator.

20. The method of claim 19, wherein the evaluating step comprises DNA sequencing or immunohistochemical analysis.

21. The method of claim 14, wherein the cancer is further characterized by unwanted glycolysis.

22. The method of claim 14, wherein the cancer is further characterized by unwanted glutamine uptake.

23. The method of claim 14, wherein the method further comprises subjecting the patient in need thereof to a second anti-cancer therapeutic treatment selected from the group consisting of radiation therapy, chemotherapy, hormonal therapy or treatment with a targeted cancer compound.

24. The method of claim 23, said second treatment is selected from the group consisting of treatment with taxotere, mitoxantrone, anti-androgen therapy, radiation, anti-estrogen therapy, xeloda, 5-FU, adriamycin, cytoxan, taxol, taxotere, avastin, herceptin, temodar and tarceva.

25. The method of claim 14, wherein the cancer is cancer of the colon, lung, pancreas, prostate, breast or brain.

26. The method of claim 14, wherein the patient is suffering from at least one tumor caused by the cancer.

16. (canceled)

17. The method of claim 16, wherein the AMPK activator is phenformin.

23-1. The method of claim 14, wherein the method further comprises subjecting the patient in need thereof to a second anti-cancer therapeutic treatment selected from the group consisting of radiation therapy, chemotherapy, hormonal therapy or treatment with a targeted cancer compound.

24-2. The method of claim 23, said second treatment is selected from the group consisting of treatment with taxotere, mitoxantrone, anti-androgen therapy, radiation, anti-estrogen therapy, xeloda, 5-FU, adriamycin, cytoxan, taxol, taxotere, avastin, herceptin, temodar and tarceva.

25-3. The method of claim 14, wherein the cancer is cancer of the colon, lung, pancreas, prostate, breast or brain.

26-4. The method of claim 14, wherein the patient is suffering from at least one tumor caused by the cancer.

27. A method of promoting apoptosis of a cell characterized as having an aberrant EGFR or KRAS genotype, comprising contacting the cell with an AMPK activator.

28. The method of claim 27, wherein the AMPK activator is a direct activator.

29. (canceled)

30. The method of claim 29, wherein the AMPK activator is phenformin.

31. The method of claim 27, wherein the cell is a cancer cell.

32. The method of claim 31, wherein the cancer is cancer of the colon, lung, pancreas, prostate, breast or brain.

33. The method of claim 32, wherein the AMPK activator is used in conjunction with another anti-cancer agent.

34. The method of claim 33, wherein the method further comprises subjecting the characterized cell to a second anti-cancer therapeutic treatment selected from the group consisting of radiation therapy, chemotherapy, hormonal therapy or treatment with a targeted cancer compound.

35. The method of claim 34, wherein said second treatment is selected from the group consisting of treatment with taxotere, mitoxantrone, anti-androgen therapy, radiation, anti-estrogen therapy, xeloda, 5-FU, adriamycin, cytoxan, taxol, taxotere, avastin, herceptin, temodar and tarceva.

27-5. A method of promoting apoptosis of a cell characterized as having an aberrant EGFR or KRAS genotype, comprising contacting the cell with an AMPK activator.

28-6. The method of claim 27, wherein the AMPK activator is a direct activator.

29-7. The method of claim 27, wherein the AMPK activator is an indirect activator.

30-8. The method of claim 29, wherein the AMPK activator is phenformin

31-9. The method of claim 27, wherein the cell is a cancer cell.

32-10. The method of claim 31, wherein the cancer is cancer of the colon, lung, pancreas, prostate, breast or brain.

33-11. The method of claim 32, wherein the AMPK activator is used in conjunction with another anti-cancer agent.