My laboratory is the lead laboratory in the Neuro-Oncology
Program of the Duke Comprehensive Cancer Center. The
Neuro-Oncology Program is one program that bridges
the gap between basic and clinical sciences. The goals
of my laboratory are to study basic mechanisms of
neoplastic transformation and mechanisms of altered
growth control in malignant brain tumors and tumors
that metastasize to the brain and spinal cord. The
members of the Program do preclinical studies to define
ways to translate their basic findings into better
methods of diagnosis and treatment.
Primary activities that take place in the Neuro-Oncology
Program include the following: a systemic cytogenetic
study of common brain tumors, ongoing studies of childhood
gliomas and ependymomas, in depth study and identification
of many of the amplified oncogenes in nervous system
tumors. Based upon information from the cytogenetic
studies, we are now seeking the presence of new suppressor
genes on chromosome 10 in adult human gliomas.
Our laboratory has had a long interest in the use
of monoclonal antibodies for targeted therapy. The
most well developed is an antibody against parts of
the tenascin extracellular matrix molecule, which
is present on most primary brain tumors and many metastatic
tumors but not on normal brain. This antibody is presently
in Phase I clinical trial and yielding promising results.
Molecular genetic engineering to produce smaller antibody
fragments is being employed.
The third major research area in the program is one
of new drug discovery and mechanisms of drug resistance.
In this program several new drugs not previously known
to be active against central nervous system tumors
have been discovered and are currently in Phase I
trial, both for neoplastic meningitis and for intra-arterial
therapy to intra-cranial neoplasms. Future major program
focuses will be in applying many of the findings of
basic research to pre-clinical and clinical work in
gene therapy and tumor vaccines.
