Methods for novel drug discovery, treatment and selective targeting for gefitinib-resistant non-small-cell lung cancer harboring T790M mutation

Patent metadata

Field	Value
Publication number	US-9439898-B2
Application number	US-201414296477-A
Country	US
Kind code	B2
Filing date	Jun 5, 2014
Priority date	Apr 22, 2014
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

The present invention relates to methods for novel drug discovery, treatment and selective targeting for Gefitinib-resistant non-small-cell lung cancer (NSCLC) harboring an additional mutation, in particular, to the discovery of a drug candidate or agent identified by the presently claimed method for use in treating and selective targeting Gefitinib-resistant NSCLC harboring T790M mutation.

First claim

What is claimed is:

1. A method for examining cytotoxic potency of a compound or chemical agent for selectively inducing cytotoxicity in Gefitinib-resistant non-small-cell lung cancer harboring T790M mutation comprising providing Gefitinib-resistant non-small-cell lung cancer cells harboring said mutation or transfecting into normal cells with an expression vector containing a construct of epidermal growth factor receptor having said mutation; applying an effective amount of said compound or chemical agent to either said cancer cells or normal cells transfected with said expression vector,
wherein the cytotoxic potency of said compound or chemical agent is indicated by an elevating level of reaction oxygen species through up-regulation and activation of NOX3 which triggers degradation of epidermal growth factor receptor and leads to apoptosis of said cancer cells.

2. The method of claim 1 , wherein said compound is sanguinarine.

3. The method of claim 1 , wherein said chemical agent is hydrogen peroxide.

4. The method of claim 1 , wherein said cancer cells are H1975 cells.

5. The method of claim 1 , wherein said normal cells are HEK293 cells.

6. The method of claim 1 , wherein said construct of epidermal growth factor receptor having said mutation has a coding sequence of SEQ. ID NO. 1.

7. The method of claim 1 , wherein said epidermal growth factor receptor with the T790M mutation has an amino acid sequence of SEQ. ID. NO. 2.

8. The method of claim 1 , wherein said compound is a methionine reductase inhibitor.

9. The method of claim 1 , wherein said compound is a NOX3 activator.

Assignees

• Univ Macau Sci & Tech

Inventors

• Leung Elaine Lai-Han
• Liu Liang
• Fan Xing-Xing

Classifications

• G01N2333/90209

  acting on NADH or NADPH (1.6), e.g. those with a heme protein as acceptor (1.6.2) (general), Cytochrome-b5 reductase (1.6.2.2) or NADPH-cytochrome P450 reductase (1.6.2.4) · CPC title

• A61K31/4741 Primary

  condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title

• A61K33/40

  Peroxides · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title