Refining Therapeutic Decisions and Predicting Drug Efficacy
The genetics of disease and of a patient's inherent metabolic processes influence therapeutic effectiveness, and the propensity of that patient to adverse drug reactions. Single gene markers of disease have already been applied successfully to therapeutic decisions in cancer, most notably in prescribing targeted therapies such as Herceptin® for breast cancer patients with Her2 over-expression.



Likewise, the importance of pharmacogenomics markers has been demonstrated through the correlation of specific genetic variations in the CYP450 family of genes to drug metabolism of many major drug classes. As a Powered by Affymetrix™ partner, Roche Diagnostics has commercialized the first microarray-based diagnostic for such variants, the AmpliChip CYP 450 Test, on the Affymetrix Molecular Diagnostics platform.

Used in clinical trials, GeneChip® array profiling can predict patient response to novel therapies, providing a route for development of safer and more effective courses of treatment. To date, there are over 40 such examples of the application of GeneChip® microarrays in clinical trials. A recent Phase III clinical trial by Novartis Pharmaceuticals used expression profiles to predict the success or failure of Gleevec™ treatment on chronic myelogenous leukemia patients. They analyzed gene expression patterns from patients prior to treatment and found a 31 gene ?No Response? signature, which predicts a 200-fold higher probability of failed therapy.

Similarly, in a Phase II clinical trial conducted at the Dana Farber Cancer Research Institute for the Millenium Pharmaceutical drug Velcade™, researchers used GeneChip arrays to collect pharmacogenomic data from myeloma patients treated with the drug. The scientists discovered a pattern consisting of 30 genes that correlate with response or lack of response to therapy. Clinical utility of biomarkers will be further assessed in a Phase III trial.

In the near future, DNA polymorphism information generated using Affymetrix's DNA array products will have similar clinical trial applications.