Oncogene NRF2

Patent metadata

Field	Value
Publication number	US-10337071-B2
Application number	US-200913055697-A
Country	US
Kind code	B2
Filing date	Jul 15, 2009
Priority date	Jul 25, 2008
Publication date	Jul 2, 2019
Grant date	Jul 2, 2019

Abstract

The present invention provides a marker which can be used as an indicator for efficacy prediction of an mTOR related anticancer agent or prognostic prediction, and a novel anticancer agent. The present invention provides a method for efficacy evaluation of a cancer drug, and, specifically, a prediction method for the efficacy of an mTOR-related cancer drug by detecting NRF2 abnormality. In addition, the present invention provides a prognostic prediction method for cancer, and, specifically, a prediction method for the prognosis of cancer by detecting NRF2 abnormality. Furthermore, the present invention provides a novel anticancer agent that targets NRF2.

First claim

The invention claimed is:

1. A method to identify and treat cancer susceptible to treatment with an mTOR inhibitor or a P13K inhibitor in a subject which method comprises:
(a) preparing DNA from a cancer sample originated from the subject;
(b) hybridizing DNA contained in the cancer sample with primers that amplify DNA that comprises a mutation in a sequence that encodes NRF2 protein but can not amplify DNA without said mutation, and amplifying DNA that comprises the mutation;
(c) detecting the amplified DNA to determine the presence of DNA with the mutation; and
wherein said DNA with the mutation encodes an NRF2 protein wherein
tryptophan at position 24 of SEQ ID NO:2 is replaced with a different amino acid;
glutamine at position 26 of SEQ ID NO:2 is replaced with a different amino acid;
isoleucine at position 29 of SEQ ID NO:2 is replaced with a different amino acid;
leucine at position 30 of SEQ ID NO:2 is replaced with a different amino acid;
glycine at position 31 of SEQ ID NO:2 is replaced with a different amino acid;
glutamine at position 75 of SEQ ID NO:2 is replaced with a different amino acid;
aspartic acid at position 77 of SEQ ID NO:2 is replaced with a different amino acid;
glutamic acid at position 79 of SEQ ID NO:2 is replaced with a different amino acid;
threonine at position 80 of SEQ ID NO:2 is replaced with a different amino acid; or
glutamic acid at position 82 of SEQ ID NO:2 is replaced with a different amino acid; and
(d) administering to said subject whose cancer DNA comprises said mutation an mTOR inhibitor and/or a PI3K inhibitor.

2. The method of claim 1 wherein in said NRF2 protein
tryptophan at position 24 of SEQ ID NO:2 is replaced by cysteine or lysine;
glutamine at position 26 of SEQ ID NO:2 is replaced by glutamic acid;
isoleucine at position 28 of SEQ ID NO:2 is replaced by glycine;
leucine at position 30 of SEQ ID NO:2 is replaced by phenylalanine;
glycine at a position 31 of SEQ ID NO:2 is replaced by alanine;
glutamine at position 75 of SEQ ID NO:2 is replaced by histidine;
aspartic acid at position 77 of SEQ ID NO:2 is replaced by valine or glycine;
glutamic acid at position 79 of SEQ ID NO:2 is replaced by lysine;
threonine at position 80 of SEQ ID NO:2 is replaced by lysine or proline; or
glutamic acid at position 82 of SEQ ID NO:2 is replaced by aspartic acid.

Assignees

• Shibata Tatsuhiro
• Saito Shigeru
• Nat Cancer Ct
• Infocom Corp

Inventors

• Shibata Tatsuhiro
• Saito Shigeru

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• Y10T436/143333

  Saccharide [e.g., DNA, etc.] · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title