Lipid scavenging in Ras cancers

Patent metadata

Field	Value
Publication number	US-10130600-B2
Application number	US-201414890106-A
Country	US
Kind code	B2
Filing date	May 9, 2014
Priority date	May 10, 2013
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

Methods and compositions for treating Ras-related cancers are provided that involve targeting lipid scavenging. Methods and compositions for identifying and/or characterizing more or less responsive cancers are also provided.

First claim

What is claimed is:

1. A method of identifying and/or characterizing an agent useful for the treatment of a Ras-driven cancer and/or a hypoxic tumor by determining its effect on lipid scavenging as compared with an appropriate control, wherein the step of determining comprises
contacting a population of tumor cells with at least one test agent;
incubating the cells in the presence of a medium comprising serum, labelled glucose, and labelled glutamine;

measuring amount of labelled fatty acid in the tumor cells;
measuring amount of unlabelled fatty acid in the tumor cells; and
identifying and/or characterizing the at least one test agent for its ability to alter cellular uptake of fatty acids relative to uptake by an otherwise identical cell or tissue that is not cancerous.

2. The method of claim 1 , wherein the cells are immortalized Baby Mouse Kidney (iBMK) cells.

3. The method of claim 1 , wherein the lipid is polyunsaturated.

4. The method of claim 1 , wherein the lipid is a phospholipid.

5. The method of claim 1 , wherein the lipid is a lysophospholipid.

6. The method of claim 1 , wherein the labelled fatty acid comprises 13 C.

7. The method of claim 1 , wherein the labelled fatty acid is labelled by metabolism of U- 13 C-glucose and/or U- 13 C-glutamine.

8. The method of claim 1 , wherein the tumor cells are incubated in a medium having an O 2 level of 1% or less.

9. The method of claim 1 , wherein the tumor cells are incubated in a medium having an O 2 level of 0.5% or less.

Assignees

• Memorial Sloan Kettering Cancer Center
• Univ Princeton

Inventors

• Rabinowitz Joshua
• Kamphorst Jurre
• Thompson Craig
• Cross Justin

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

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

• A23L33/10 Primary

  using additives (addition of substantially indigestible substances A23L33/21) · CPC title

• G01N33/57575

  involving oncogenic proteins · CPC title