Methods for predicting response of triple-negative breast cancer to therapy
View Patent ↗The present invention provides compositions and methods for detecting the expression and/or activation levels of components of signal transduction pathways in tumor cells such as triple-negative metastatic breast tumor cells. Information on the expression and/or activation levels of components of signal transduction pathways derived from use of the present invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.
1. A method for determining whether a human subject with a triple-negative breast cancer will respond to therapy with a combination of bevacizumab (Avastin®), carboplatin, and paclitaxel, the method comprising:
(a) obtaining a breast tumor sample from the human subject;
(b) determining an expression profile in said sample of VEGFR2 protein, c-KIT protein, HER1 protein, and IGF-1R protein using a proximity immunoassay by contacting the sample with (1) capture antibodies that bind to each of VEGFR2 protein, c-KIT protein, HER1 protein, and IGF-1R protein, and (2) detection antibodies comprising first and second activation state-independent antibodies that bind to each of VEGFR2 protein, c-KIT protein, HER1 protein, and IGF-1R protein, wherein the capture antibodies are attached to a solid support, wherein the first activation state-independent antibodies are labeled with glucose oxidase, wherein the second activation state-independent antibodies are labeled with horseradish peroxidase, and wherein the binding of the first and second activation state-independent antibodies in proximity to each other generates a detectable signal;
(c) comparing said expression profile to a reference expression profile comprising a median expression level of VEGFR2 protein, c-KIT protein, HER1 protein, and IGF-1R protein in a human population of triple-negative breast tumors; and
(d) determining whether the human subject with a triple-negative breast cancer will respond to therapy with a combination of bevacizumab (Avastin®), carboplatin, and paclitaxel based on altered expression of VEGFR2 protein, c-KIT protein, HER1 protein, and IGF-1R protein in the sample relative to the reference expression profile, wherein decreased expression of VEGFR2 protein relative to the median expression level of VEGFR2 protein, decreased expression of c-KIT protein relative to the median expression level of c-KIT protein, increased expression of HER1 protein relative to the median expression level of HER1 protein, and decreased expression of IGF-1R protein relative to the median expression level of IGF-1R protein is indicative of response to therapy with the combination of bevacizumab (Avastin®), carboplatin, and paclitaxel.
2. The method of claim 1 , wherein the triple-negative breast cancer is triple-negative metastatic breast cancer.
3. The method of claim 1 , wherein the paclitaxel is a nanoparticle albumin-bound (nab) paclitaxel.