Dr Donna Hansel on Targeting mTOR in Advanced Bladder Cancer

mTOR is a very promising pathway because it’s so central in growth, migration, and survival of bladder cancer cells, explained Donna Hansel, MD, PhD, chief, anatomic pathology, UC San Diego.

Transcript

Advanced bladder has limited therapeutic options when conventional therapy has failed. How does your lab approach the identification of targetable pathways for advanced bladder cancer?

So, my lab focuses primarily on the mammalian target of rapamycin, or mTOR, signaling pathway, and we know from The Cancer Genome Atlas (TCGA) data that was produced that a very large number of bladder cancers, advanced bladder cancers, have some sort of alteration that affects signaling through the mTOR pathway. Despite some initial trials looking at mTOR inhibition, we feel it’s a very promising pathway because it’s so central in growth, in migration, in survival of bladder cancer cells, that we’ve continued to study it.

What we’ve done is to focus on 2 aspects of mTOR signaling and to try and understand what happens downstream from it, because it’s very likely that if we understand more about the mTOR pathway, that includes both mTORC1 and mTORC2, we’ll be able to better define potentially more actionable targets that we could find downstream.

So, for example, focusing on mTORC2, which has been a big passion of my lab members, we have now identified approximately 50 downstream targets, novel targets, that do affect migration, and do affect invasion. In bladder cancer, it’s critical to understand that invasive pathway that leads to higher local stages, but it’s also important to understand how invasion and interaction with the endothelial cells then leads to metastasis. We’re finding more and more information studying mTORC2 that indeed there are a number of very unique regulators downstream that affect both of these pathways, and all of which are quite actionable.