Targeted Therapy, Biomarkers and Imaging Sub-Program

This Sub-Program is grounded in the strength of the basic science programs in the discovery, analysis, and validation of molecular targets important for cancer. Such targets can be exploited for therapy, detection, diagnosis, and for the assessment of responses to intervention, and thus there is a common scientific foundation for the therapeutic and analytic (biomarker and imaging) components of this Sub-Program.

Theme 1: Targeted Therapy

Scientists at the University of Virginia have pioneered many of the fundamental discoveries in signal transduction, and have differentiating expertise in tyrosine kinase receptors, mTor, and intracellular protein kinases.  A number of recent clinical trials have been and are being initiated based on this expertise. Christopher Y. Thomas, IV, M.D., an expert on squamous cell carcinomas of head and neck, is conducting research on drug interventions as well as evaluation of signal transduction markers."  Head and neck cancers over-express the EGF Receptor, and preliminary laboratory and clinical studies suggest: 1) that this receptor drives the cancer; and 2) that inhibiting it will be therapeutically beneficial in a subset of patients. Because the tumors are accessible to repeated biopsy, this group of diseases is particularly well suited for studies on targeted therapies, where molecular analysis of tumor samples, and customization of treatment for disease subsets, is key to success.

Theme 2: Biomarkers

Scientists at the University of Virginia have been leaders in the deployment of mass spectroscopy for the analysis of protein sequences, and this expertise is now being applied to the search for biomarkers of cancer risk and prognosis. Dan Theodorescu, M.D., Ph.D. has been using mass spectroscopy to develop urinary protein biomarkers for urothelial bladder cancer that can be used to predict tumor stage and the presence of tumor metastasis. Since the markers are proteins produced by cancer cells and/or cells in the tumor microenvironment, urine serves as the primary discovery reagent.

David Brenin, M.D. uses proteomic analysis of both nipple aspirate fluid and ductal lavage specimens obtained from patients with breast malignancies or pre-cancerous lesions in order to identify new biomarkers for breast cancer.  The ultimate goal of proteomic analysis of ductal fluid is to develop an improved breast cancer screening modality. It is hypothesized that a unique, reproducible proteomic pattern will be identifiable in patients with invasive breast cancer, DCIS, and atypical ductal hyperplasia and differs from the proteomic pattern found in fluid from non-diseased breasts. 

Christopher A. Moskaluk M.D., Ph.D. uses a broad array of molecular techniques - including proteomics and gene array analysis - to uncover molecular alterations of a variety of primary human cancers, focusing on lung and on head and neck cancers. His investigations have uncovered several genes that have been or are currently being investigated for their functional significance in cancer biology and in clinical utility. These include the up-regulation of a stem cell associated transcription factor (Sox 4) in several human cancer types, a protein that appears to confer an anti-apoptotic phenotype. The homeobox transcription factor Cdx-2 was observed to be up regulated in gastrointestinal carcinomas and shown to be an important biomarker in early stages of esophageal tumor progression. He has discovered a novel secreted gene product that is upregulated in squamous carcinoma and is currently investigating its utility as a clinical biomarker in cancer screening.

Theme 3: Imaging

Image-guided breast surgery is a project whose goal is to use a breast scanner, developed by a team led by Mark Williams, Ph.D., to guide surgeons to nonpalpable breast lesions. The scanner utilizes stereotactic x-ray and gamma emission imaging to place a small marker, labeled with a radioisotope, at the center of the lesion. The surgeon identifies the location of the marker using a hand-held gamma probe.

Paul W. Read, M.D., Ph.D., leads a research group which is developing improvements in extracranial image guided stereotactic radiation therapy (SRT) for head and neck cancer. They have been developing a helical tomotherapy-based program at this institution.  SRT is the treatment of small cancerous lesions with 1-5 fractions of high dose-per-fraction conformal radiation therapy. They are performing dosimetric studies comparing a helical tomotherapy-based system to more conventional LINAC-based systems to determine how their system compares to commercially available planning and delivery systems.