Compositions and methods of treating cancer

Patent metadata

Field	Value
Publication number	US-9801922-B2
Application number	US-201214236879-A
Country	US
Kind code	B2
Filing date	Aug 2, 2012
Priority date	Aug 3, 2011
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The invention provides compositions and methods to treat cancer with an agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria (“an XTPP agent”) or a pharmaceutically acceptable salt thereof, an inhibitor of hydroperoxide metabolism and a pharmaceutically acceptable diluent or carrier.

First claim

What is claimed is:

1. A method for treating lung cancer in a mammal, comprising administering to the mammal a pharmaceutical composition comprising a decyl-TPP agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria, an inhibitor of hydroperoxide metabolism, and a pharmaceutically acceptable diluent or carrier.

2. The method of claim 1 , wherein the composition does not significantly inhibit viability of comparable non-cancerous cells.

3. The method of claim 1 , wherein the cancer is reduced in volume by at least 10% as compared to a non-treated cancer.

4. The method of claim 3 , wherein tumor uptake of a molecular imaging agent is reduced by any amount between 1-100% as compared to a non-treated cancer.

5. The method of claim 4 , wherein the imaging agent is fluorine-18 deoxyglucose, fluorine-18 thymidine or other suitable molecular imaging agent.

6. The method of claim 1 , wherein the composition is administered intraveneously, orally, subcutaneously, as an aerosol, or by means of another approved mode of pharmaceutical administration.

7. The method of claim 6 , wherein the composition is administered at a dosage of 5-200 micromol/kg/day of decyl-TPP agent agent.

8. The method of claim 1 , wherein the inhibitor of hydroperoxide comprises L-buthionine-[S,R]sulfoximine (BSO).

9. The method of claim 1 , further comprising feeding the mammal a ketogenic diet.

10. The method of claim 1 , further comprising administering pharmacological doses of IV vitamin C.

11. A method for inducing cellular apoptosis or clonogenic cell killing of a cancerous lung cell, comprising contacting the cancerous lung cell with an effective toxicity-inducing amount a composition comprising a decyl-TPP agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria, an inhibitor of hydroperoxide metabolism, and a pharmaceutically acceptable diluent or carrier.

12. The method of claim 11 , wherein the inhibitor of hydroperoxide comprises L-buthionine-[S,R]sulfoximine (BSO).

13. A method for increasing the anticancer effects of a lung cancer therapy on a cancerous lung cell in a mammal, comprising contacting the cancerous cell with an effective amount of the composition comprising a decyl-TPP agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria, an inhibitor of hydroperoxide metabolism, and a pharmaceutically acceptable diluent or carrier, and contacting prior to administering an additional cancer therapy.

14. The method of claim 13 , wherein the inhibitor of hydroperoxide comprises L-buthionine-[S,R]sulfoximine (BSO).

15. A method for inducing oxidative stress in a lung cancer cell in a mammal in need of such treatment comprising administering to the mammal an effective amount of the composition comprising a decyl-TPP agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria, an inhibitor of hydroperoxide metabolism, and a pharmaceutically acceptable diluent or carrier.

16. The method of claim 15 , wherein the inhibitor of hydroperoxide comprises L-buthionine-[S,R]sulfoximine (BSO).

Assignees

• Spitz Douglas R
• Schultz Michael K
• Kloepping Kyle
• Zhu Yueming
• Aykin-Burns Nukhet
• Wicha Max S
• Univ Iowa Res Found
• Univ Michigan

Inventors

• Spitz Douglas R
• Schultz Michael K
• Kloepping Kyle
• Zhu Yueming
• Aykin-Burns Nukhet
• Wicha Max S

Classifications

• A61K38/17 Primary

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• A61K45/06

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

• A61K31/41

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title