A Molecular Profile of Colorectal Cancer to Guide Therapy [HMEC]

Here we describe the generation and application of a gene expression signature for the Rheb pathway. Affymetrix array data obtained from human mammary epithelial cells over expressing Rheb or GFP were used to generate a Rheb/mTOR activation signature. To test the capacity of the signature to predict patient response to everolimus we treated patient-derived colorectal cancer explants (PDCCEs) predicted to have high and low Rheb pathway activity withthe mTOR inhibitor everolimus. This study utilized a total of 20 affymetrix data files generated from 20 independent human mammary epithelial cell culture samples treated with adenovirus overexpressing either Rheb (n=10) or GFP (n=10). From these data, a Rheb gene expression signature was created and used to predict Rheb/mTOR activity in patient derived colorectal cancer explants (PDCCEs). PDCCEs were then tested for response to the mTOR inhibitor everolimus.