Drug selection for colorectal cancer therapy using receptor tyrosine kinase profiling

Patent metadata

Field	Value
Publication number	US-10401364-B2
Application number	US-201715636534-A
Country	US
Kind code	B2
Filing date	Jun 28, 2017
Priority date	Feb 3, 2011
Publication date	Sep 3, 2019
Grant date	Sep 3, 2019

Abstract

The present invention provides methods for selecting a suitable anticancer drug therapy, and for identifying and predicting response, for the treatment of colorectal cancer. The present invention also provides methods for monitoring the status of colorectal cancer and monitoring how a patient with colorectal cancer is responding to anticancer drug therapy. The present invention further provides methods for the rational selection of therapy with one or more anticancer drugs tailored to target signal transduction pathway components with dysregulated expression and/or activation levels in patients with somatic mutations in an oncogene.

First claim

What is claimed is:

1. A method for determining whether a combination of anticancer drugs targeting cMET and IGF1R should be administered for the treatment of colorectal cancer (CRC) in a subject with CRC and having cancer cells with a KRAS mutation, the method comprising:
(a) lysing cancer cells with a KRAS mutation isolated from the subject to produce a cellular extract;
(b) detecting the expression level and/or activation level of cMET and the expression level of IGF1R in the cellular extract using an immunoassay, wherein the immunoassay is a Collaborative Enzyme Enhanced Reactive Immunoassay; and
(c) determining that the combination of anticancer drugs targeting cMET and IGF1R should be administered to the subject when a higher expression level and/or activation level of cMET and a higher expression level of IGF1R is detected compared to an expression level and/or activation level of cMET and an expression level of IGF1R in a cellular extract from cancer cells with wild-type KRAS isolated from a subject with CRC.

2. The method of claim 1 , further comprising detecting the expression level and/or activation level of one or more FGFRs, VEGFRs, and combinations thereof.

3. The method of claim 1 , wherein the KRAS mutation is selected from the group consisting of G12S, G12D, G12A, G12V, G12R, G12C, G13D, and combinations thereof.

4. The method of claim 1 , wherein the cancer cells are circulating tumor cells (CTCs) or fine needle aspirate (FNA) cells obtained from a colorectal tumor.

5. The method of claim 4 , wherein the tumor is primary tumor tissue or metastatic tumor tissue.

6. The method of claim 1 , further comprising detecting the expression level and/or activation level of one or more ErbB RTKs.

7. The method of claim 6 , wherein the expression level and/or activation level of the one or more ErbB RTKs is higher in the cellular extract from the cancer cells with the KRAS mutation as compared to a reference expression level and/or activation level of the same ErbB RTKs.

8. The method of claim 7 , further comprising determining that an anticancer drug targeting one or more ErbB RTKs should be administered to the subject.

9. The method of claim 6 , wherein the one or more ErbB RTKs is selected from the group consisting of HER1, HER2, HER3, HER4, and combinations thereof.

10. The method of claim 1 , wherein the anticancer drugs are selected from the group consisting of a monoclonal antibody, a tyrosine kinase inhibitor, an antiproliferative agent, a chemotherapeutic agent, and combinations thereof.

Assignees

• Nestec Sa
• Soiete Des Produits Nestle S A

Inventors

• Kim Phillip
• Singh Sharat

Classifications

• G01N33/57535 Primary

  of the large intestine, e.g. colon, rectum or anus · CPC title

• G01N2333/91205

  Phosphotransferases in general · CPC title

• G01N2333/71

  for growth factors; for growth regulators · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/57419 Primary

  Physics · mapped topic