Breast cancer is the second leading cause of death among women in the United States. In 2008, an estimated 182,460 new cases will be diagnosed and 40,480 women will die of breast cancer.
HER 2 is a receptor tyrosine kinase oncogene product over-expressed in 30% of breast cancers. HER 2 targeted therapy (Trastuzumab®) has been FDA approved for breast cancer. The extracellular form (ECD) of HER 2 is shed into serum and HER 2 testing has been approved by the FDA to identify eligible metastatic breast cancer patients for Trastuzumab® treatment and follow-up and monitoring of patients with metastatic breast cancer. The promise of personalized medicine in breast cancer is not only to be able to recruit patients for target specific therapy but also to monitor subsequent treatment effectiveness.
In this work, we demonstrate the capability of our Lab-on-a-chip (LOC) multi-analyte biosensor platform in tailoring to the needs of the personalized medicine cancer diagnostics arena. For this proof-of-concept study, we have developed a first generation companion diagnostics chip for HER 2. We also demonstrate multiplexing ability of our platform with a proof-of-concept multiplex assay of HER 2 with CA 125 (prognostic marker for ovarian cancer).
The LOC sensor array platform performs chemical and immunological reactions on and within the interior regions of micro-spheres positioned in the inverted pyramidal micro-chamber wells of a silicon microchip. Micro-fluidic structures deliver a series of small-volume reagents and washes to the chip and to each of the micro-spheres. Optical signals generated by the reactions on the microspheres are visualized by, a charge-coupled device (CCD) video chip along with the use of trans-wafer optics. Using the LOC system, we have developed ultra sensitive sandwich ELISA type immunological assays for these tumor biomarkers. These immunoassays can be performed with small sample volumes and short assay times, and markedly reduced reagent costs thereby enabling rapid, cost effective analysis, imperative for realizing companion diagnostics for delivering personalized therapeutic decisions.
The assays developed have excellent analytical characteristics comparable to commercially available methods and multiplexing abilities rendering them amenable to the development of companion diagnostics in cancer therapy. Future work will entail clinical validation of the assay developed. The lab-on-a-chip platform lends itself to other analyte classes and hence promises a multiplex approach that cuts across several classes of analytes. Access to personalized medicine on such rapid and low cost LOC platforms can truly deliver the promise of fitting ‘the right drug to the right patient’ instead of a ‘one size fits all’ approach. This work will set a precedent for developing future companion diagnostics to serve along with targeted cancer therapeutics.
- American Association for Cancer Research