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Professional
/ Research Summary
Retinoblastoma
My laboratory program has aimed at characterizing retinoblastoma gene
alterations through analysis of tumor and peripheral blood specimens
from UCSF's extensive retinoblastoma patient base. |
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My
colleagues and I have been working to define the nature of the mutations
that arise in retinoblastoma patients, toward the goal of developing
rapid, cost-effective genetic testing. We have also been exploring
deregulation in downstream genetic and biochemical pathways, which
may render patients susceptible to a variety of other secondary cancers
throughout their lifetimes; early diagnosis of second tumor predisposition
is a goal of this research, since the mortality from second tumors
is 45% at 35 years. If retinoblastoma patients are given radiation
treatments, which are generally very effective in eliminating the
primary tumor in the eye, this treatment may also cause alterations
in other genetic loci, rendering them less capable of regulating cell
growth. Subsequently, second cancers, such as osteosarcomas, arise
within the radiation field of these patients.
Developing New Treatments and Therapies for Retinoblastoma.
Current work on transgenic murine retinoblastoma, and related in vitro
studies, emphasizes the examination of outcomes of various single
and combination treatment modalities. In particular, we are exploring
alternative treatments for retinoblastoma which could minimize visual
compromise, agent toxicity and long-term second tumor risk. Our hope
is that these results may be generalized to developing new treatments
for human retinoblastoma.
Work on transgenic models originated with my efforts to characterize
an SV40T-antigen expressing genetic model of retinoblastoma and subsequent
work using chimeric mice. Ongoing studies (with Bruce Ksander, PhD,
Schepens Eye Research Institute, Harvard Medical School) are examining
various aspects of immune modulation and immune therapy for retinoblastoma
and metastatic choroidal melanoma.
Multidisciplinary Approach to Cancer Management.
In my clinical practice, I have established a multidisciplinary approach
to the evaluation of retinoblastoma patients seen at UCSF. In a single
visit to the multidisciplinary clinic, the patient and family may
consult with physicians and other health care professionals from all
disciplines involved in that patient's care. This clinic has provided
an additional benefit to patients who are already receiving intensive
individual care, and has fostered enhanced cooperation in support
of research. We have also initiated the development of an easily accessed
digital database, combining patient information that is relevant to
research, clinical and administrative requirements.
Stemming from my collaboration in a clinical chemotherapy study (with
Helen Chan, MD and Brenda Gallie, MD, of Toronto Sick Children's Hospital),
I have reported clinical data to the National Institutes of Health
on the application of chemotherapy in retinoblastoma, in an attempt
to avoid radiation in these children predisposed to develop second
tumors within their radiation fields. UCSF was named a steering institute
for the Retinoblastoma Study, an international multi-center clinical
trial of chemotherapy protocols. In addition, I have also proposed
a clinical trial of adjuvant chemotherapy treatment for patients with
histopathologically determined high risk retinoblastoma. Preliminary
data and discussion are scheduled for publication in early 2001. .
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