Use of NF-κB inhibition in combination therapy for cancer

• US 6,831,057 B2
• Filed: 10/28/1997
• Issued: 12/14/2004
• Est. Priority Date: 10/28/1997
• Status: Expired due to Term

• Current Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Baldwin, Albert S., Mayo, Marty W., Wang, Cun-Yu, Cusack, James C.
• Primary Examiner(s): MCKELVEY, TERRY ALAN
• Application Number:
  US08/959,160
• Publication Number:
  US 20020068690A1
• Time in Patent Office: 2,604 Days
• Field of Search: 514/44, 514/2, 514/1
• US Class Current: 514/1
• 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,

and wherein said antineoplastic chemotherapeutic agent is an anthracyclene antibiotic.

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 daunorubicin, doxorubicin, mitoxantraone, and bisanthrene.

4. 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 an 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 said NF-κ

B inhibitor,

wherein said NF-κ

B inhibitor is a proteasome inhibitor,

and wherein said chemotherapeutic agent is an anthracyclene antibiotic.

5. A method according to claim 4, wherein said NF-κ

B inhibitor is administered simultaneously with said chemotherapeutic agent.

6. A method according to claim 4 wherein said chemotherapeutic agent is selected from the group consisting of daunorubicin, doxorubicin, mitoxantraone, and bisanthrene.

7. A method of treating a tumor in a mammalian subject with a chemotherapeutic agent, the improvement comprising administering an effective amount of an NF-κ

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

B inhibitor,

wherein said NF-κ

B inhibitor is a proteasome inhibitor,

and wherein said chemotherapeutic agent is an anthracyclene antibiotic.

8. A method of treating a mammalian subject receiving a chemotherapeutic agent for the treatment of a neoplastic growth, the improvement comprising administering an effective amount of an NF-κ

B inhibitor to the subject in conjunction with said chemotherapeutic agent, wherein the effect is to increase the cytotoxic effects of said chemotherapeutic agent,

wherein said NF-κ

B inhibitor is a proteasome inhibitor,

and wherein said chemotherapeutic agent is an anthracyclene antibiotic.

9. A method of increasing the cytotoxicity of a chemotherapeutic agent administered to a mammalian subject for the treatment of a neoplastic growth, comprising administering an effective amount of an NF-κ

B inhibitor to said subject in conjunction with said chemotherapeutic agent, wherein the effect is to increase the cytotoxic effects of said chemotherapeutic agent,

wherein said NF-κ

B inhibitor is a proteasome inhibitor,

and wherein said chemotherapeutic agent is an anthracyclene antibiotic.

10. The method of claim 9, wherein said chemotherapeutic agent is doxorubicin.

11. The method of claim 9, wherein said neoplastic growth is breast cancer.

12. The method of claim 9, wherein said chemotherapeutic agent is doxorubicin and said neoplastic growth is breast cancer.