- My name is Ana Ruiz-Saenz, I am a post-doctoral scientist
at UCSF. And I work in a lab in which we study the molecular
mechanisms that drive tumor formation and cancer
progression. 

- And in particular we are interested in a type
of cancer, a type of breast cancer that is named
HER2-amplified breast cancer. And in the case of
HER2-amplified cancers, the main driver of the disease is
known HER2. There is massive expression of the protein HER2
in the surface of the cancer cells. This cancer not only
affects a significant number of women but is a cancer that
is associated with poor outcomes. 

And understanding the biology that is driving tumor
formation is essential to design better treatment for these
patients. 

- So it's known that HER2 has been the driver of the
disease and for that reason, over the years a lot of effort
have been placed in developing inhibitors for HER2. And one
of these inhibitors is a well known targeted therapy that is
called Herceptin. So this antibody is meant to block the
activity of HER2 and has been definitely a game changer for
the patients who have HER2-amplified cancers. For a lot of
drugs in the clinic cancer cells develop resistance. 

- But the way that HER2 works is not by itself. One of the key players
of mechanisms of resistance is HER3. The way that these
proteins work is by interacting with each other forming what
we called a dimer. So when they form a dimer, they activate
each other and they can signal pathways inside the cell that
lead to growth and survival of the cancer cells. But
unfortunately, HER3 right now remains undruggable. And a lot
of effort are placed to develop an inhibitor for HER3 in
many laboratories, in companies and some of these inhibitors
are right now in clinical trials. 

- So in our lab, we wanted to interrogate how cancer cells
would respond to those HER3 inhibitors once they are there.
If HER2 has been the game changer, will HER3 really be the
end for HER2-amplified cancers. So the idea was to inject
these cancer cells lacking HER3 expression into mice and
wait and see if the mice developed tumors. The expected
outcome was that those cells were unable to form tumors and
that is what is known. But what we did in this experiment is
to push out the limit and monitor the tumor growth of these
mice for longer than was done before. But if you wait
enough, you get to see the result. The cancer cells were
finding a way to overcome the requirement of HER3.