Personalized therapy of inflammation-associated cancer using methods of assessing the susceptibility of a subject to the treatment with EGFR inhibitors/antagonists
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.
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.
2. The method of claim 1 , wherein the subject is a human.
3. The method of claim 1 , wherein greater than 10% of myeloid cells in the myeloid cell population detectably express EGFR.
4. The method of claim 3 , wherein greater than 20% of myeloid cells in the myeloid cell population detectably express EGFR.
5. The method of claim 4 , wherein greater than 30% of myeloid cells in the myeloid cell population detectably express EGFR.
6. The method of claim 1 , wherein the sample is a cancer tissue biopsy sample.
7. The method of claim 1 , wherein the myeloid cells are CD68-positive macrophage cells.
8. The method of claim 1 , wherein the inflammation-associated cancer is hepatocellular carcinoma.
9. The method of claim 1 , wherein the sample is a liver tissue sample.
10. The method of claim 1 , wherein the myeloid cells are Kupffer cells.
11. The method of claim 1 , wherein the inflammation-associated cancer is colorectal cancer.
12. The method of claim 11 , wherein the sample is a colorectal tissue sample or a colorectal polyp.
13. The method of claim 1 , wherein the myeloid cells are identified by determining a level of translation of EGFR therein.
14. The method of claim 13 , wherein the level of translation is determined using an immunohistochemical method, an enzyme-linked immunosorbent assay, or a radioimmunoassay.
15. 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.