BETA - What is a Selective Inhibitor of Nuclear Export? (SINE)

[Music] what is a selective inhibitor of nuclear export or sign so sell an excerpt is a very exciting new drug it's a first in-class agent which means it's a novel mechanism of action we don't have any other drugs in this category and what's really interesting about this is it's not just myeloma and the reason I think it was published in New England Journal is there are other tumors that are also being studied including lymphoma sarcoma endometrial cancer and so what it brings up then is that cancer cells have a shuttle protein that moves proteins from the brains of the celled a nucleus into the cytoplasm and those proteins are very important for cell growth and division and basically survival and there are three main categories of those are tumor suppressor proteins so these are the breaks of the cells that prevent the cells from growing and often cancer cells are smart they they pump those breaks out of the brain and then the brain can grow and do its thing and basically this is like a sedative for the brain because it stops that pump and then these tumor suppressors breaks are retained in the nucleus where they stop the cell from growing the second category proteins are called uncle proteins and so these are proteins that help the cell grow and these were also blocked from being going moving into the from the brain into the cytoplasm and the third protein is the glucocorticoid receptor everybody's favorite drug steroids is actually moved from the brains of the cell into the cytoplasm and by blocking that you all of the these three protein categories that are retained in the nucleus results in the cell death and so I think what's exciting about this is it's amazing that it's working in myeloma but the fact that it applies to other tumors tells that this is a general cancer mechanism right so many cancer cells are utilizing this mechanism to prevent cell death and avoid resist and avoid chemotherapy killing cell and XOR is what's called a sign a selective inhibitor of nuclear export now if you try to imagine a cell and inside the cell there's a nucleus and between the nucleus and the rest of the cell they're little holes called export ins and they're chemicals that go inside and outside of the nucleus and part of these help regulate when the cell is allowed to die and when it's not so when a cell becomes cancerous it kicks out the proteins that allow it to survive so it says I can ignore the signals of the body telling me to kill myself but what this drug does selling XO is it blocks these export ins and traps those chemicals in the nucleus so when the body tells it as a cancer cell to undergo programmed cell death what we call apoptosis the cell can't ignore it anymore and is forced to undergo the cell death and not proliferating cause more cancer [Music]