The discussion centered around emergent biomarkers and targeted therapies in NSCLC, exploring targets like CEACAM5, TROP2, HER3, cMET, and the potential role of antibody drug conjugates in refractory disease.
Joshua Sabari: Now, outside of molecular driver alterations, we talked about PD-L1 and if patients are PD-L1 high or low, we'll hear from Dr. Florez in a moment about treatment. But there are also other biomarkers that are now becoming critical. Take it away Dr. Florez. What are some of the sort of standard of care in the frontline setting? What are some of the novel biomarkers that are coming down the pipeline? For our patients with non-small cell lung cancer?
Narjust Florez: One of the things about lung cancer research is moving fast. When we finally get one, then we get four new biomarkers. Let's talk about CEACAM5 first, because that is the main character of our conversation today. You may know about CEACAM5 for CEA. CEA has been used in colon cancer since 1960. The CEA is the result of CEACAM5, which is a glycoprotein that is expressed mostly in your plastic tissue [00:06:00] and epithelial cells. Something about CEACAM5 that I found very interested is only seen in primates. It hasn't been seen in other species as I - us, and is related to two things. We're going to talk a little bit more about that but it's related to cell adhesion, proliferation, and differentiation and apoptosis. That's one of the emerging biomarkers. We're going to decode that later. But there's other major biomarkers including TROP2. Which is trophoblast cell surface antigen two. This is a transmembrane glycoprotein particularly seen in epithelial cells. We don't have a target yet for TROP2. It's under development with dato-DXd, highest pressure TROP2 has been associated with poor prognosis. Then we have HER3. HER3 is like the sequence of HER2. I hope sequences are as good. So is this breast and 40% of patients we know this way most lung cancer. HER3 is known to be a resistant mechanism for patients that have EGFR mutations that go on EGFR directed therapy. Also, HER3 contributes to metastatic development, and also to these resistant mechanisms. Finally, another emerging biomarker is cMET not to be confused with MET14 skipping mutations, cMET is mostly the combination of the cMETHGF axis, which is the ligand is the hepatocyte growth factor, cMET is that tyrosine kinase receptor that's currently under development. And we're going to continue to hear about this new emerging biomarker. It's also known to be a resistant mechanism for some targeted therapies. To summarize some of the emerging biomarkers includes CEACAM5, TROP2, HER3, cMET. I can tell you, Bradley, we're going to record these next year. We're going to have a few more to talk about.
Joshua Sabari: So definitely an exciting time Dr. Florez. Thinking again, not just looking at histology to guide therapy. Not just thinking about a molecular alteration, the guy therapy. But now we're looking at cell surface markers, protein expression, to try to understand can we target cancer in a different way. Five or six already pretty prime time. Markers that we're starting to look at. Obviously, all of these therapies are currently under clinical development and are not currently were yet FDA approved. But really, I think an exciting time.