Interview
with Neil Love, MD from Breast Cancer Update for Medical Oncologists,
Program 5 2000
Play
Audio Below:
TKs
share kind of general set of motifs. They’re all, as a group,
on the cell membrane, as opposed say, to the steroid receptor, which
is a nuclear receptor. Typically they’ll all have an external
membrane domain, and that is a ligand-binding domain. So, for instance,
heregulin will bind to HER3 or HER4, transforming growth factor
alpha will bind to the external membrane domain of the epidermal
growth factor receptor. They have a very short transmembrane component
and then they’ll have an internal membrane domain that has
the tyrosine kinase function. Once ligand binding has occurred,
this results in a conformational change in the receptor that activates
the tyrosine kinase and leads to a cascade of intracellular events.
Now, which intracellular event occurs depends upon what tyrosine
kinase is being activated, but in general I think it’s safe
to say that most of the aspects of the malignant phenotype that
we’re familiar with — I think, such as invasion, growth,
production of proangiogenic factors — occur as a result of
cascades that start with tyrosine kinases.
Biological
rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody
therapy [Review]. Pegram, M. and Slamon, D Seminars in Oncology.
27(5 Suppl 9):13-19, 2000 Oct.
In
process Current and planned clinical trials with trastuzumab (Herceptin)
[Review]. Baselga, J. Seminars in Oncology. 27(5 Suppl 9):27-32, 2000
Oct. In process
Clinical
trials of single-agent trastuzumab (Herceptin) [Review]. Seminars in Oncology. 27(5 Suppl 9):20-26, 2000 Oct. In proces
