Biomarkers for radiation treatment

Abstract

The methods described herein allow for the classification of patients into groups for receiving optimized radiation treatment based on patient specific biomarker signature. The biomarker signature includes markers that have been shown to correlate with TGF-B expression and to be associated with tumor aggressiveness, radioresistance and poor prognosis. The markers play a key role in the epithelial-mesenchymal transition. The methods described herein provide the dual benefits of anti-tumor efficacy plus normal tissue protection when combining TGF-B inhibitors with ionizing radiation to treat cancer patients.

What is claimed is: 
     
         1 . A method of identifying a subject as a candidate for treatment with ionizing radiation, comprising:
 (a) determining an expression level of two or more biomarkers in a tumor sample from the subject, wherein the one or more biomarkers are selected from the group consisting of CD44, MMP9, ALDH1A1, Vimentin, hyaluman, beta-catenin, MFG-E8 and CD68; and   (b) comparing the expression level of the two or more biomarkers to an expression level in a normal tissue sample;   wherein an expression level of the two or more biomarkers in the tumor sample that is modified compared to the expression level in the normal tissue sample identifies the subject as a candidate for treatment with ionizing radiation.   
     
     
         2 . The method of  claim 1 , wherein the expression level of the two of more biomarkers is ranked or weighted. 
     
     
         3 . The method of  claim 1 , wherein the expression level of biomarkers CD44 and CD68 is increased in the tumor environment. 
     
     
         4 . The method of  claim 1 , wherein the tumor sample is a biopsy comprising tumor cells. 
     
     
         5 . The method of  claim 1 , wherein the normal tissue sample comprises non-tumor cells from the same tissue type as the tumor. 
     
     
         6 . The method of  claim 1 , wherein the biomarker is a gene, an RNA, or a protein and the expression level is determined by detecting the expression of an RNA and/or a protein. 
     
     
         7 . The method of  claim 6 , wherein the detecting is selected from the group consisting of immunohistochemistry, ELISA, Western analysis, HPLC, proteomics, PCR, RT-PCR, Northern analysis, and nucleic acid or polypeptide microarrays. 
     
     
         8 . The method of  claim 1 , further comprising treating the subject with ionizing radiation if the expression level of the two or more biomarkers in the tumor sample is modified compared to the expression level in the normal tissue sample. 
     
     
         9 . The method of  claim 8 , wherein the treatment further comprises contacting the tumor with a radiosensitizer. 
     
     
         10 . The method of  claim 8 , wherein the treatment further comprises administering a compound that inhibits TGF-beta signaling to the subject. 
     
     
         11 . The method of  claim 10 , wherein the TGF-beta inhibitor is an antibody or a small molecule that neutralizes or inhibits TGF-beta function, or the TGF-beta inhibitor inhibits the production of TGF-beta. 
     
     
         12 . A method for selecting a treatment for a subject having a tumor, comprising:
 (a) determining an expression level of two or more biomarkers in a tumor sample from the subject, wherein the two or more biomarkers are selected from the group consisting of CD44, MMP9, ALDH1A1, Vimentin, hyaluronan, beta-catenin, MFG-E8 and CD68;   (b) comparing the expression level of the two or more biomarkers to an expression level in a normal tissue sample; and   selecting a treatment if the expression level of the two or more biomarkers is modified compared to the expression level in the normal tissue sample.   
     
     
         13 . The method of  claim 12 , wherein the expression level of biomarkers CD44 and CD68 is increased in the tumor environment. 
     
     
         14 . The method of  claim 12 , wherein the tumor sample is a biopsy comprising tumor cells. 
     
     
         15 . The method of  claim 12 , wherein the normal tissue sample comprises non-tumor cells from the same tissue type as the tumor. 
     
     
         16 . The method of  claim 12 , wherein the treatment comprises administering ionizing radiation to the tumor. 
     
     
         17 . The method of  claim 16 , wherein the treatment further comprises contacting the tumor with a radiosensitizer. 
     
     
         18 . The method of  claim 16 , wherein the treatment further comprises administering a compound that inhibits TGF-beta signaling to the subject. 
     
     
         19 . The method of  claim 18 , wherein the TGF-beta inhibitor is an antibody or a small molecule that neutralizes or inhibits TGF-beta function, or the TGF-beta inhibitor inhibits the production of TGF-beta. 
     
     
         20 . A kit comprising reagents capable of detecting expression of a biomarker selected from the group consisting of CD44, MMP9, ALDH1A1, Vimentin, hyaluronan, beta-catenin, MFG-E8 and CD68.