The Role of BRAF Mutations in Melanoma

Source:OncLive, September 2019

My name is Adil Daud. I’m a medical oncologist. I work at the University of California, San Francisco, where I direct melanoma research and the melanoma program.

The role of BRAF mutations in melanoma is an interesting 1, and it’s a switch that’s present in melanoma cells. And if you think about the cell machinery, there are a lot of on-off switches in the cell. And BRAF is 1 of those switches that can be in an on position or an off position. When you have a BRAF mutation like the V600E or V600K mutation, that’s like having a switch jammed in the on position. And normally the cell is able to turn off when there’s a lack of external signals; it’s able to turn on when there are more external signals, but once you have that mutation, the cell is not able to turn off. And so it keeps on dividing and keeps on growing. That’s the significance of the BRAF mutation.

It has a long history, melanoma. When it was first found, what was interesting was that a lot of benign moles—you know, I have a whole bunch of them—a lot of moles also have BRAFmutations. And so people were kind of surprised that something that is present at such an early stage of melanoma development—you know, right at that stage where you have benign moles—seems to be so important in late-stage or advanced-stage melanoma. In cell lines, if you use a BRAF inhibitor, it definitely causes significant shrinkage in tumors in mice and in culture. And when patients were tested with BRAF inhibitors, which was back in 2008 and 2009, patients were noticed to have dramatic response. Like marked responses—like within a month or 2, tumors were half in size.