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Welcome everybody to this talk
on receptor tyrosine
kinase signaling
and the targeted
therapies thereof.
Today we're going to
focus particularly
on two receptor
tyrosine kinases,
some downstream
signaling pathways
that are important in cancer,
initiation in
cancer progression,
those being eGFR and then
its partner in crime, HER2.
By way of introduction,
my name is Mike Wendt,
I'm an associate professor
here at the College of
Pharmacy at Purdue
University in Indiana.
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The learning objectives for
today will be to understand
the basic concepts involved
in kinase signaling,
briefly review the idea
of the transferring of
of gamma phosphate on ATP
to a substrate molecule via
the action of a kinase.
We'll want to understand
the fundamental concepts,
or components of major
pathways activated
activated by receptor tyrosine
kinase (RTK) signaling.
We'll focus mostly on two
major downstream pathways
and some targeted
therapies thereof.
We want to be able to
connect the concepts of
mutational activation,
molecular diagnostics,
leading to the application
of targeted therapies
that we discussed.
This is really a
personalized medicine and
represents a beautiful
synergy between genetics,
medicinal chemistry,
and then the clinical
application of these therapies.
Finally, we will
understand some successes
of combination therapies,
we'll briefly visit the
idea of combining some of
the kinase inhibitors
that we'll talk about
and the successes and
potential failures thereof.
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Kinases are highly prevalent
molecules in the genome.
Nearly 500 kinases have
been characterized
throughout our genome.
Based on sequence similarity,
potentially 900
kinases might exist.
If we look at this dendrogram,
we can see that a large
family of these kinases
are indeed these
tyrosine kinases.
Molecules that transfer
a gamma phosphate from
ATP onto a tyrosine residue
of a substrate molecule.
A large part of these
tyrosine kinase families is
those kinases that lie
on the plasma membrane,
and therefore are receptor
tyrosine kinases.
A very important large
class of molecules
that become dysregulated
during cancer,
leading to things associated
with cancer progression.
Things like proliferation,
increased survival,
migration and so
on and so forth.
