METHODS FOR PREDICTING A PATIENT'S RESPONSE TO EGFR INHIBITORS
The present invention provides methods for individualizing chemotherapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to an EGFR inhibitor, such as an EGFR tyrosine kinase inhibitor or a molecule targeting the extracellular domain of EGFR. The method generally comprises culturing malignant cells from a patient's specimen (e.g., biopsy specimen), contacting the cultured cells with an EGFR inhibitor that is a candidate treatment for the patient, and evaluating the cultured cells for a response to the drug. In certain embodiments, monolayer(s) of malignant cells are cultured from explants prepared by mincing tumor tissue, and the cells of the monolayer are suspended and plated for chemosenstivity testing. The in vitro response to the drug as determined by the method of the invention is correlative with the patient's in vivo response upon receiving the EGFR inhibitor during chemotherapeutic treatment (e.g., in combination with other standardized or individualized chemotherapeutic regimen).
1 . A method for predicting a patient's response to an epidermal growth factor receptor (EGFR) inhibitor, comprising:
culturing malignant cells from said patient;
contacting the cultured cells with an EGFR inhibitor, and evaluating the cultured cells for a cytotoxic response, wherein the cytotoxic response is indicative of the patient's response to the EGFR inhibitor.
2 . The method of claim 1 , wherein the EGRF inhibitor is an EGFR tyrosine kinase inhibitor.
3 . The method of claim 1 , wherein the EGFR inhibitor targets the extracellular domain of EGFR.
4 . The method of claim 2 , wherein the EGFR tyrosine kinase inhibitor is erlotinib, gefitinib, or lapatinib.
5 . The method of claim 3 , wherein the EGFR inhibitor is cetuximab or panitumumab.
6 . The method of claim 1 , wherein the patient has lung cancer.
7 . The method of claim 6 , wherein the patient has non-small cell lung cancer (NSCLC).
8 . The method of claim 1 , wherein the patient has colorectal cancer.
9 . The method of claim 1 , wherein the patient has head and neck cancer.
10 . The method of claim 1 , wherein the patient has breast cancer.
11 . The method of claim 1 , wherein the patient has previously received a first line of chemotherapy.
12 . The method of claim 7 , wherein the patient is a non-smoker.
13 . The method of claim 12 , wherein the patient has never been a smoker.
14 . The method of claim 1 , wherein the patient has pancreatic cancer.
15 . The method of claim 1 , wherein the cultured cells are enriched for malignant cells.
16 . The method of claim 15 , wherein the cultured cells are from monolayers grown from multicellular particulates of tumor tissue.
17 . The method of claim 16 , wherein the multicellular particulates are prepared by mincing the tumor tissue.
18 . The method of claim 16 , wherein the multicellular particulates are agitated to release malignant cells, and/or the multicellular particulates are removed from the monolayer at about 20% to about 70% confluency.
19 . The method of claim 16 , wherein the multicellular particulates have a size of from about 0.25 to about 1.5 mm 3 .
20 . The method of claim 16 , wherein the multicellular particulates have smooth cut edges.
21 . The method of claim 1 , wherein the malignant cells are contacted with a range of doses of said EGFR inhibitor.
22 . The method of claim 21 , further comprising preparing a dose response curve for said EGFR inhibitor.
23 . The method of claim 1 , further comprising, indicating whether said patient will be responsive, non-responsive, or intermediately responsive to said EGFR inhibitor, or indicating whether said cultured cells were responsive, non-responsive, or intermediately responsive to said EGFR inhibitor.