There's a foundation, called the Breast Cancer Research Foundation that
supports clinical trials and genetic studies in breast cancer. Every year they
have a symposium in New York that's open to the public, where people can come
every year to present their various findings.
The E1A is one of the
targets that was discussed at that particular symposium. This isn't research
that I was involved in directly, but it was part of the research that I'm
involved in peripherally because of the activities of the Breast Cancer Research
Foundation. It is one of the components of the signaling pathway in the cell
that tells the cell to divide. It's a very complicated matrix of chemical
reactions that tells the cell to divide.
A cell can be stimulated to
start to divide because estrogen acts on the estrogen receptor or HER-2 is
stimulated. That's a much more complicated story, or other signals start at the
cell surface. But then there's a cascade of events that eventually leads to cell
division. That's called signal transduction, where the signal is transduced to a
number of events, and this is a component of that particular process. That's
also a potential target for therapeutics, and there's a variety of different
ways for approaching that particular target.
Ansomycins
The HER-2 molecule -- that thing on the
surface of the cell -- like every other molecule in the body, has to be made,
but it has to be folded in a certain way for it to be functional. The body just
doesn't make the chemicals, it has to actually fold the chemicals and put them
in the right configuration. The way this chemical folds is that there are a
class of proteins in the cell called chaperone proteins, the function of which
is to hold the molecule in the right position so it can fold properly. And there
is a certain class of chaperone molecules that are called heat-shock proteins.
Well, we have a drug that gets into the heat-shock protein, and prevents the
HER-2 from getting there. So the HER-2 can't fold correctly, and when it doesn't
fold correctly, the body, the cell, destroys it. These drugs, which are called
ansomycins, actually make the cell destroy its own HER-2. So, not only can you
attack HER-2 by interfering with the HER-2 itself, with some drug like
Herceptin®, or interfere with the functioning or the reproduction of the HER-2
with targets, which is E1A, but you can also actually destroy the HER-2 in the
cell by preventing the body, the cell, from folding it properly. These drugs are
called ansomycins, and they're actually in clinical trial right now. There's one
other drug called 17-AEG that we're studying that actually does that. It looks
profoundly exciting and actually kills cancer cells beautifully in the
laboratory, and now we're doing the clinical studies to see if it
works.
