DRUG SELECTION FOR CANCER THERAPY BY PROFILING SIGNAL TRANSDUCTION PROTEINS IN ASCITES OR PLEURAL EFFLUX SAMPLES
The present invention provides methods for selecting a suitable anticancer therapy and for identifying and predicting response for the treatment of a gastric cancer by determining the expression level and/or activation level of one or more analytes in a cell such as a cancer cell from an ascites sample. The present invention also provides methods for selecting a suitable anticancer therapy and for identifying and predicting response for the treatment of a lung cancer such as a non-small cell lung cancer by determining the expression level and/or activation level of one or more analytes in a cell such as a cancer cell from a pleural efflux sample.
1 . A method for selecting a suitable anticancer drug for the treatment of a gastric cancer, the method comprising:
(a) determining the expression level and/or activation level of one or more analytes selected from the group consisting of HER1, HER2, p95HER2, HER3, c-Met, IGF1R, cKit, PI3K, Shc, Akt, p70S6K, VEGFR, PDGFR, and combinations thereof in a cancer cell from an ascites sample; and
(b) selecting a suitable anticancer drug for the treatment of the gastric cancer based upon the expression level and/or activation level of said one or more analytes determined in step (a).
2 . The method of claim 1 , wherein the expression level and/or activation level of said one or more analytes is calibrated against a standard curve generated for said one or more analytes.
3 . The method of claim 1 , wherein the cancer cell is lysed to produce a cellular extract.
4 . The method of claim 1 , wherein the cancer cell is stimulated in vitro with one or more growth factors.
5 . The method of claim 1 , wherein the cancer cell is isolated from the sample.
6 . The method of claim 5 , wherein the cancer cell is isolated after administration of an anticancer drug.
7 . The method of claim 5 , wherein the isolated cancer cell is contacted with an anticancer drug.
8 . The method of claim 6 , wherein the suitable anticancer drug is selected by comparing the expression level and/or activation level of said one or more analytes to a reference expression and/or activation profile of said one or more analytes that is generated in the absence of the anticancer drug.
9 . The method of claim 1 , wherein the sample is obtained from a subject with gastric cancer.
10 . The method of claim 1 , wherein step (a) comprises determining the expression level and/or activation level of any combination of two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen of said one or more analytes.
11 . The method of claim 1 , wherein said one or more analytes comprises at least HER1, HER2, HER3, PI3K, and/or c-Met.
12 . The method of claim 1 , wherein said one or more analytes comprises at least HER1, HER2, HER3, c-Met, IGF1R, PI3K, Shc, and/or cKit.
13 . The method of claim 1 , wherein the anticancer drug is selected from the group consisting of a monoclonal antibody, tyrosine kinase inhibitor, anti-proliferative agent, chemotherapeutic agent, and combinations thereof.
14 . The method of claim 1 , wherein step (a) comprises determining both the expression level and activation level of said one or more analytes.
15 . The method of claim 1 , further comprising determining the expression level and/or activation level of one or more additional analytes in the cancer cell.
16 . The method of claim 1 , wherein step (a) comprises determining the expression level and/or activation level of said one or more analytes with a Collabotrative Enzyme Enhanced Reactive Immunoassay (CEER).
17 . A method for identifying the response of a gastric cancer to treatment with an anticancer drug, the method comprising:
(a) determining the expression level and/or activation level of one or more analytes selected from the group consisting of HER1, HER2, p95HER2, HER3, c-Met, IGF1R, cKit, PI3K, Shc, Akt, p70S6K, VEGFR, PDGFR, and combinations thereof in a cancer cell from an ascites sample; and
(b) identifying the response of the gastric cancer to treatment with an anticancer drug based upon the expression level and/or activation level of said one or more analytes determined in step (a).
18 . A method for selecting a suitable anticancer drug for the treatment of a lung cancer, the method comprising:
(a) determining the expression level and/or activation level of one or more analytes selected from the group consisting of HER1, HER2, p95HER2, HER3, c-Met, IGF1R, cKit, PI3K, Shc, Akt, p70S6K, VEGFR, PDGFR, and combinations thereof in a cancer cell from a pleural efflux sample; and
(b) selecting a suitable anticancer drug for the treatment of the lung cancer based upon the expression level and/or activation level of said one or more analytes determined in step (a).
19 - 34 . (canceled)
35 . A method for identifying the response of a lung cancer to treatment with an anticancer drug, the method comprising:
(a) determining the expression level and/or activation level of one or more analytes selected from the group consisting of HER1, HER2, p95HER2, HER3, c-Met, IGF1R, cKit, PI3K, Shc, Akt, p70S6K, VEGFR, PDGFR, and combinations thereof in a cancer cell from a pleural efflux sample; and
(b) identifying the response of the lung cancer to treatment with an anticancer drug based upon the expression level and/or activation level of said one or more analytes determined in step (a).
36 . The method of claim 7 , wherein the suitable anticancer drug is selected by comparing the expression level and/or activation level of said one or more analytes to a reference expression and/or activation profile of said one or more analytes that is generated in the absence of the anticancer drug.