Development of Successful Biomarkers:  Our Experience & Capabilities

DNA Biomarkers

• PIK3CA Mutations in Human Tumors
  In her capacity as CSO for BioMarker Strategies, Dr. Murphy developed a novel assay to detect mutations in the PIK3CA gene, which occur in a variety of human cancers.  This assay has been designed to be highly effective in formalin-fixed paraffin-embedded tissues.  She has also worked closely with Dr. Clark to optimize the pre-analytical processing of human biopsy samples for this assay and clinical test.  This assay, which is being performed in a CLIA-certified laboratory, was utilized to stratify patients for eligibility in a Johns Hopkins-based clinical trial.
  

•  FLT3 Mutations as a Target for Novel FLT3 Kinase Inhibitor Therapy
  In her capacity as Director of the Molecular Diagnostics Laboratory at Johns Hopkins, Dr. Murphy developed a novel assay to detect mutations in the FLT3 gene, which occur frequently in patients with acute myeloid leukemia (AML).  Although these mutations generally portend a worse prognosis for AML patients, they may also be the Achilles heal of the disease.  New therapies targeted at the FLT3 gene have been developed and are currently in clinical trials at Johns Hopkins and elsewhere.  The assay developed by Dr. Murphy was used at Johns Hopkins and other institutions to qualify patients to participate in these clinical trials. 

Protein Biomarkers 

• Proteins Expressed in Cervical Disease
  In his position at Johns Hopkins, Dr. Clark developed, along with a corporate sponsor, a novel immunocytochemical assay for cervical cancer. This assay utilizes antibodies to detect two proteins (TOP2A and MCM2) that are over-expressed in cervical cancer and its precursors in cervical cytology samples. This biomarker assay is being used in a large, multi-center, US, in-vitro diagnostic study.
  

RNA-based Biomarkers 

• Gene Expression Profile to Detect Response to Targeted Therapy
  In his position at Johns Hopkins, Dr. Clark developed an RNA-based assay to detect the pharmacologic actions of EGFR inhibitors (Gefitinib and Erlotinib) on tumor samples from patients with solid tumors. This assay is designed to measure the levels of the early response mRNA, c-fos, which is decreased in sensitive tumor cells treated with gefitinib or erlotinib. This assay and related assays are being utilized in oncology clinical trials at Johns Hopkins.

•  Identification of Immunocytochemical Biomarkers for Papillary Thyroid Carcinoma Using Gene Expression Profiling
  Dr. Clark and Dr. Murphy have successfully utilized gene expression profiling to identify novel biomarkers associated with the solid thyroid tumor, papillary thyroid carcinoma.