Use of NF-kB inhibition in combination therapy for cancer

• US 20050123506A1
• Filed: 11/02/2004
• Published: 06/09/2005
• Est. Priority Date: 10/28/1997
• Status: Active Grant

• Current Assignee: Albert S. Baldwin, Cun-Yu Wang, James C. Cusack, Marty W. Mayo
• Original Assignee: Albert S. Baldwin, Cun-Yu Wang, James C. Cusack, Marty W. Mayo
• Inventors: Baldwin, Albert S., Mayo, Marty W., Wang, Cun-Yu, Cusack, James C.
• Granted Patent: US 7,700,543 B2
• Time in Patent Office: Days
• US Class Current: 424/85.100
• 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 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/191 Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta

Abstract

The use of NF-κB inhibitors to enhance the cytotoxic effects of chemotherapy or radiation therapy in the treatment of neoplastic conditions is described.

Claims

1. A method of enhancing the cytotoxic effects of an antineoplastic chemotherapeutic agent, comprising administering to a mammalian subject in need of said antineoplastic chemotherapeutic agent a therapeutically effective amount of NF-κ

B inhibitor in conjunction with the administration of the chemotherapeutic agent, whereby the cytotoxic effect of said chemotherapeutic agent is increased compared to that which would occur in the absence of NF-κ

B inhibitor,

wherein said NF-κ

B inhibitor is a proteasome inhibitor.

2. A method according to claim 1 wherein said NF-κ

B inhibitor is administered simultaneously with said chemotherapeutic agent.

3. The method of claim 1 where said chemotherapeutic agent is selected from the group consisting of vinka alkaloids, epipodophyllotoxins, anthracyclene antibiotics, actinomycin D, plicamycin, puromycin, gramicidin D, paclitaxel, colchicine, cytochalasin B, emetine, maytansine, amsacrine, cisplatin, carboplatin, mitomycin, altretamine, cyclophosphamide, lomustine, carmustine, and irinotecan.

14. A method according to claim 1, wherein said subject is afflicted with lung, breast prostate, brain, kidney, liver, spleen, pancreas, bone or muscle cancer.

16. A method according to claim 1, wherein said subject is afflicted with leukemia or lymphoma.

4-5. -5. (canceled)

6. A method of enhancing chemotherapeutic cytotoxicity in a mammalian subject treated with an antineoplastic chemotherapeutic agent, comprising administering to the mammalian subject a therapeutically effective amount of NF-κ

B inhibitor in conjunction with the administration of the chemotherapeutic agent, whereby the cytotoxic effect of said chemotherapeutic agent is increased compared to that which would occur in the absence of NF-κ

B inhibitor,

wherein said NF-κ

B inhibitor is a proteasome inhibitor.

7. A method according to claim 6 wherein said NF-κ

B inhibitor is administered simultaneously with said chemotherapeutic agent.

8. A method according to claim 6 wherein said chemotherapeutic agent is selected from the group consisting of vinka alkaloids, epipodophyllotoxins, anthracyclene antibiotics, actinomycin D, plicamycin, puromycin, gramicidin D, paclitaxel, colchicine, cytochalasin B, emetine, maytansine, amsacrine, cisplatin, carboplatin, mitomycin, altretamine, cyclophosphamide, lomustine, carmustine, and irinotecan.

15. A method according to claim 6, wherein said subject is afflicted with lung, breast prostate, brain, kidney, liver, spleen, pancreas, bone or muscle cancer.

17. A method according to claim 6, wherein said subject is afflicted with leukemia or lymphoma.

9-13. -13. (canceled)