Methods for treating brain metastasis

Patent metadata

Field	Value
Publication number	US-12029717-B2
Application number	US-202117345572-A
Country	US
Kind code	B2
Filing date	Jun 11, 2021
Priority date	Sep 19, 2014
Publication date	Jul 9, 2024
Grant date	Jul 9, 2024

Abstract

The present invention relates to methods for treating brain metastasis by inhibiting gap junction functionality. It is based, at least in part, on the discovery that cancer cells expressing Protocadherin 7 and Connexin 43 form gap junctions with astrocytes that promote the growth of brain metastases, and that inhibition of Protocadherin 7 and/or Connexin 43 expression in cancer cells reduce progression of brain metastases. It is further based on the discovery that treatment with gap junction inhibitors tonabersat and meclofenamate inhibited progression of brain metastatic lesions and enhanced the anti-cancer activity of the conventional chemotherapeutic agent, carboplatin.

First claim

What is claimed is:

1. A method for treating a subject having a cancer that has metastasized to the brain, comprising administering meclofenamate or a salt form thereof to the subject.

2. The method of claim 1 , wherein the meclofenamate or salt form thereof is a sodium salt form of meclofenamate.

3. The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer and lung cancer.

4. The method of claim 1 further comprising administering, to the subject, a therapeutically effective amount of an anti-cancer agent.

5. The method of claim 4 , wherein the anti-cancer agent is carboplatin.

6. The method of claim 1 , wherein the subject was known to have one or more brain metastases prior to treatment.

7. The method of claim 1 , wherein one or more cancer cells of the subject express Connexin 43 and/or Protocadherin 7.

8. A method for treating brain metastasis in a subject having a cancer, comprising administering meclofenamate or a salt form thereof to the subject.

9. The method of claim 8 , wherein the meclofenamate or salt form thereof is a sodium salt form of meclofenamate.

10. The method of claim 8 , wherein the cancer is selected from the group consisting of breast cancer and lung cancer.

11. The method of claim 8 , further comprising administering, to the subject, a therapeutically effective amount of an anti-cancer agent.

12. The method of claim 11 , wherein the anti-cancer agent is carboplatin.

13. The method of claim 8 , wherein one or more cancer cells of the subject express Connexin 43 and/or Protocadherin 7.

14. A method of reducing the risk of detectable metastasis of a cancer to the brain in a subject, comprising administering meclofenamate or a salt form thereof to the subject.

15. The method of claim 14 , wherein the meclofenamate or salt form thereof is a sodium salt form of meclofenamate.

16. The method of claim 14 , wherein the cancer is selected from the group consisting of breast cancer and lung cancer.

17. The method of claim 14 further comprising administering, to the subject, a therapeutically effective amount of an anti-cancer agent.

18. The method of claim 1 , wherein the meclofenamate or salt form thereof is administered in an amount between about 1 mg/kg to about 30 mg/kg.

19. The method of claim 8 , wherein the meclofenamate or salt form thereof is administered in an amount between about 1 mg/kg to about 30 mg/kg.

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• Massague Joan
• Boire Adrienne
• Chen Qing

Classifications

• A61K31/353 Primary

  3,4-Dihydrobenzopyrans, e.g. chroman, catechin · CPC title

• G01N2333/705

  Assays involving receptors, cell surface antigens or cell surface determinants · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title

• A61K31/282

  Platinum compounds · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title