Inhibitor of the shh signalling patway and a testosterone supressing agent for the treatment of cancer

• US 20060094660A1
• Filed: 09/17/2003
• Published: 05/04/2006
• Est. Priority Date: 09/17/2002
• Status: Abandoned Application

• Current Assignee: Medical Research Council (Government of United Kingdom)
• Original Assignee: Medical Research Council (Government of United Kingdom)
• Inventors: Thomson, Axel Andreas
• Application Number:
  US10/528,267
• Publication Number:
  US 20060094660A1
• Time in Patent Office: Days
• US Class Current: 514/10.2
• 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 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/28 : Antiandrogens
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

A method of protecting a patient from possible adverse effects of a treatment involving inhibition of the SHH-signalling pathway in the patient, the method comprising suppressing testosterone or its effect in the patient. A method of treating a proliferative disease such as cancer in a patient the method comprising inhibiting the SHH-signalling pathway and suppressing testosterone or its effect in the patient. Typically, the SHH-signalling pathway is inhibited using cyclopamine or a derivative thereof, and testosterone is suppressed using any one or more of a GnRH antagonist, a GnRH agonist, an androgen antagonist or a Sa-reductase inhibitor.

Claims

1. A method of protecting a patient from possible adverse effects of a treatment involving inhibition of the SHH-signalling pathway in the patient, the method comprising suppressing testosterone or its effect in the patient.

24. A method according to claim 1 wherein the SHH-signalling pathway is inhibited by the administration of cyclopamine or a derivative thereof to the patient.

25. A method according to claim 1 wherein testosterone is suppressed to castrate levels.

26. A method according to claim 1 wherein testosterone or its effect is suppressed by administering any one or more of a GnRH antagonist, a GnRH agonist, an androgen antagonist or a 5α

reductase inhibitor to the patient.

27. A method according to claim 1 wherein the patient is male.

28. A method according to claim 1 wherein the treatment is for a cancer in which SHH-signalling plays a role in its growth and/or differentiation.

29. A method according to claim 1 wherein the treatment is for any of basal cell carcinoma, medulloblastoma, glioblastoma, or prostate cancer.

2. A method of treating a proliferative disease in a patient the method comprising inhibiting the SHH-signalling pathway and suppressing testosterone or its effect in the patient.

3. A method according to claim 2 wherein the SHH-signalling pathway is inhibited by the administration of cyclopamine or a derivative thereof to the patient.

4. A method according to claim 2 wherein testosterone is suppressed to castrate levels.

5. A method according to claim 2 wherein testosterone or its effect is suppressed by administering any one or more of a GnRH antagonist, a GnRH agonist, an androgen antagonist or a 5α

reductase inhibitor to the patient.

6. A method according to claim 2 wherein the patient is male.

7. A method according to claim 2 wherein the proliferative disease is a cancer in which SHH-signalling plays a role in its growth and/or differentiation.

8. A method according to claim 2 wherein the proliferative disease is any of basal cell carcinoma, medulloblastoma, glioblastoma or prostate cancer.

9-17. -17. (canceled)

18. A therapeutic system for treating a patient, the system comprising an inhibitor of the SHH-signalling pathway and a compound which suppresses testosterone or its effect in the patient.

19. A composition comprising an inhibitor of the SHH-signalling pathway and a compound which suppresses testosterone or its effect in a patient.

20. (canceled)

21. A pharmaceutical composition comprising an inhibitor of the SHH-signalling pathway and a compound which suppresses testosterone or its effect in a patient and a pharmaceutically acceptable carrier.

22-23. -23. (canceled)