# US 10,309,966 B2 · Personalized therapy of inflammation-associated cancer using methods of assessing the susceptibility of a subject to the treatment with EGFR inhibitors/antagonists

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- Number: US 10,309,966 B2
- Document ID: US10309966B2
- Status: Granted
- Kind: B2
- Application number: 15/312,252
- Filed: 2015-05-21
- Published: 2017-06-29
- Granted: 2019-06-04
- Earliest claimed: 2014-05-22
- Assignees: Medizinische Universität Wien
- Applicants: Medizinische Universität Wien
- Inventors: Maria Sibilia
- Web page: https://patentgrep.com/patent/US10309966B2

## CPC

- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- G01N 33/57525: of the liver or pancreas
- G01N 2333/71: for growth factors; for growth regulators
- G01N 2800/50: Determining the risk of developing a disease
- G01N 2800/7095: Inflammation
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to in vitro methods of assessing the susceptibility or responsiveness of a subject to the treatment with an epidermal growth factor receptor (EGFR) inhibitor/antagonist, wherein the subject has been diagnosed or suspected of suffering from inflammation-associated cancer. These methods comprise determining the level of expression of EGFR in myeloid cells in a sample from the subject, wherein an expression of EGFR in the myeloid cells is indicative of the subject being susceptible to the treatment with an EGFR inhibitor/antagonist.

## Claims

### Claim 1

A method of testing a subject for the need of treatment of an inflammation-associated cancer, wherein the subject has or is suspected of having said cancer, and wherein the inflammation-associated cancer is hepatocellular carcinoma or an inflammation-associated intestinal cancer, the method comprising the steps of:
(a) obtaining a sample from the subject that comprises a myeloid cell population, wherein the myeloid cells in the myeloid cell population are CD68-positive macrophage cells and/or Kupffer cells and are from within said cancer or from the tissue adjacent to said cancer;
(b) testing the myeloid cell population to identify that portion of myeloid cells that detectably express EGFR, wherein greater than 5% of myeloid cells in the myeloid cell population detectably express EGFR; and
(c) treating the subject by administering a therapeutically effective amount of an EGFR inhibitor/antagonist to the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 3 (depends on 1)

The method of claim 1, wherein greater than 10% of myeloid cells in the myeloid cell population detectably express EGFR.

### Claim 4 (depends on 3)

The method of claim 3, wherein greater than 20% of myeloid cells in the myeloid cell population detectably express EGFR.

### Claim 5 (depends on 4)

The method of claim 4, wherein greater than 30% of myeloid cells in the myeloid cell population detectably express EGFR.

### Claim 6 (depends on 1)

The method of claim 1, wherein the sample is a cancer tissue biopsy sample.

### Claim 7 (depends on 1)

The method of claim 1, wherein the myeloid cells are CD68-positive macrophage cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein the inflammation-associated cancer is hepatocellular carcinoma.

### Claim 9 (depends on 1)

The method of claim 1, wherein the sample is a liver tissue sample.

### Claim 10 (depends on 1)

The method of claim 1, wherein the myeloid cells are Kupffer cells.

### Claim 11 (depends on 1)

The method of claim 1, wherein the inflammation-associated cancer is colorectal cancer.

### Claim 12 (depends on 11)

The method of claim 11, wherein the sample is a colorectal tissue sample or a colorectal polyp.

### Claim 13 (depends on 1)

The method of claim 1, wherein the myeloid cells are identified by determining a level of translation of EGFR therein.

### Claim 14 (depends on 13)

The method of claim 13, wherein the level of translation is determined using an immunohistochemical method, an enzyme-linked immunosorbent assay, or a radioimmunoassay.

### Claim 15 (depends on 1)

The method of claim 1, wherein the EGFR inhibitor/antagonist is selected from the group consisting of gefitinib, erlotinib, lapatinib, afatinib, neratinib, ABT-414, dacomitinib, AV-412, PD 153035, vandetanib, PKI-166, pelitinib, canertinib, icotinib, poziotinib, BMS-690514, CUDC-101, AP26113, XL647, cetuximab, panitumumab, zalutumumab, nimotuzumab, matuzumab, and a pharmaceutically acceptable salt thereof.