Protein drug target activation homogeneity in the face of intra-tumor heterogeneity: implications for precision medicine.

ABSTRACT:

Introduction

Recent studies indicated tumors may be comprised of heterogeneous molecular subtypes and incongruent molecular portraits may emerge if different areas of the tumor are sampled. This study explored the impact of intra-tumoral heterogeneity in terms of activation/phosphorylation of FDA approved drug targets and downstream kinase substrates.

Material and methods

Two independent sets of liver metastases from colorectal cancer were used to evaluate protein kinase-driven signaling networks within different areas using laser capture microdissection and reverse phase protein array.

Results

Unsupervised hierarchical clustering analysis indicated that the signaling architecture and activation of the MAPK and AKT-mTOR pathways were consistently maintained within dif

SUBMITTER: Parasido EM 

PROVIDER: S-EPMC5564706 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature