Compositions and methods for preventing and treating radiation-induced bystander effects caused by radiation or radiotherapy

Patent metadata

Field	Value
Publication number	US-11452709-B2
Application number	US-201816632046-A
Country	US
Kind code	B2
Filing date	Jul 17, 2018
Priority date	Jul 17, 2017
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

The invention provides novel compositions and methods for the treatment of Radiation-Induced Bystander Effects (RIBE), resulting from radiation exposure. In one preferred embodiment the inventions includes novel therapeutic agents, including but not limited to quercetin and quercetin analogs, as well as E64, CA074, CA074Me, that interfere with the activity of Cathepsin B.

First claim

What is claimed is:

1. A method for treating radiation-induced bystander effects (RIBE) in non-irradiated cells of a subject caused by exposure to radiation, comprising administering to the subject a therapeutically effective amount of quercetin, isoquercetin, or a combination thereof, wherein said therapeutically effective amount inhibits the activity of Cathepsin B (CTSB), preventing RIBE in said non-irradiated cells.

2. The method of claim 1 and further comprising the step of administering to the subject a therapeutically effective amount of quercetin, isoquercetin, or a combination thereof in a pharmaceutically acceptable carrier wherein said pharmaceutically acceptable carrier is an aqueous and/or non-aqueous pharmaceutically acceptable carrier.

3. The method of claim 2 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, inhibits the protease activity of CTSB.

4. The method of claim 3 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, is administered prior to the administration of the radiotherapy, along with to the administration of the radiotherapy, or after the administration of the radiotherapy.

5. The method of claim 2 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, is administered in combination with an anti-cancer therapy.

6. The method of claim 5 wherein said anti-cancer therapy is selected from the group consisting of surgery, immunotherapy, and chemotherapy, or a combination of the same.

7. The method of claim 3 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, alters cell death or cell proliferation, reduces DNA damage, or increases DNA repair in the subject.

8. The method of claim 3 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, reduces and/or prevents RIBE in a subject.

9. The method of claim 3 wherein said therapeutically effective amount of said quercetin, isoquercetin, or a combination thereof, produces at least one of the following effects in a subject:
increases the effectiveness of radiotherapy and/or chemotherapy in a cancer subject in the subject;
reduces resistance of cancer cells to radiotherapy and/or chemotherapy in the subject; and
increases the subject's tolerance to radiotherapy.

Assignees

• Univ Colorado Regents
• Univ Tsinghua
• Univ Chang Gung

Inventors

• Xue Ding
• Peng Yu
• Zhang Man
• Zheng Lingjun
• Liang Qian
• Li Hanzeng
• Yu Jau-Song
• Chen Jeng-Ting

Classifications

• G01N33/575

  for cancer · CPC title

• A61K31/353 Primary

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

• A61K31/352 Primary

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K31/4025

  not condensed and containing further heterocyclic rings, e.g. cromakalim · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title