BACKGROUND: There is an increasing application of targeted therapies to tumors based on molecular abnormalities at the DNA level (e.g. EGFR/ gefitinib or KIT/imatinib). Unfortunately, the vast majority of patients don’t carry oncogene-addicted or driven malignancies and are still treated with decades-old chemotherapies or radiothearpaies; most of these patients will not respond to the chosen treatment.
The WINTHER trial aims to increase efficacy of cancer therapeutics through an innovative clinical trial design based on a knowledge-driven systems biology combinatorial biomarker approach.
METHODS: All patients are sampled for two histologically matched biopsies (tumor and normal tissue). Each pair of samples is examined with two platforms: (1) Genomic profiling using a panel of standardized panel of informative genes (Foundation Medicine, Boston MA, USA); and (2) expression profiling using Agilent's 8x60k array (Agilent, Santa Clara CA, USA). The resulting drug prioritization reports include both a genetic alterations report, generated using a proprietary algorithm developed by Foundation Medicine, and an expression-based prioritization report, generated with a novel scoring function developed by us. The expression report is based on a knowledge-base containing a large body of evidence linking expression changes and drug efficacy which were collected from the literature. A relative efficacy score is calculated given a patients' expression profile by comparing the pattern of up/down regulation in the tumor to the expected pattern based on the knowledge-base.
RESULTS: The WINTHER is funded by the FP7 program and will take place from April 1st, 2013 up until March 31st, 2015. In the presentation we will describe the trial, explain how mutations and expression profiles are interpreted, and discuss how this approach marks a new direction in personalized cancer medicine.
Discussion: WINTHER combines a unique trial design with a state-of-the-art genomic profiling technology and a new approach to expression-based efficacy.
