Examining Molecular Targets in Sarcoma

Mark Agulnik, MD, section chief of Sarcoma Medical Oncology, Department of Medical Oncology & Therapeutics, and research professor, Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center, discusses advances in determining the molecular drivers of the tumor in the sarcoma space.

Transcription:

0:10 | Often when patients are coming to see us, the question they often have is why do they have this happening? For most sarcomas, we don't see a cause. With respect to other tumors, we may see some environmental causes, or some factors related to perhaps smoking or alcohol. The second thing is whether or not there's a genetic driver of this. I sort of piece that into 2 different compartments. One is the genetics that we're born with, and one's the genetics that we acquire over time. I often feel that for our patients there are some patients, whereby there is a genetic component with respect to the genes that are passed to them. And for me, that's often what I think of like Li-Fraumeni syndrome. Then there are acquired mutations that cause the tumors, and those are the ones that often we are searching for using different platforms like next-generation sequencing platforms.

1:05 | When we're sending off a tumor to specifically look for the genetic markers of the tumor, we're specifically looking for the drivers. I sort of categorize it into 2 different components. It's almost like a car, there's drivers and passengers. If something happens to the passenger, nothing happens to the car. But if you're able to impact the driver, then you're able to stop the car from going which is essentially stopping the tumors. We tried very hard using molecular profiles to find drivers. We've been successful with some drivers that actually do have drugs for it like and NTRK fusions.

1:41 | We also have other drivers that will mimic other diseases. So we have lung cancer, where there are several drivers that drive it. If we see the same markers in our sarcoma patients, then we will target those with lung cancer drugs. We are looking at different factors to see whether or not they would benefit from immunotherapy. All of those are reasons that we would do sequencing of our patients who have metastatic disease, to really specifically look for what is driving their tumor. If we're able to find the driver, we're able to find and tailor a therapy that's more unique to their tumor vs a therapy that would be for every patient walking in the door with the same diagnosis.