Receptor tyrosine kinase signaling and targeted therapies

Published on September 29, 2022   43 min
0:00
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.
0:29
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.
1:31
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.
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Receptor tyrosine kinase signaling and targeted therapies

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