Vemurafenib mechanism of action

Vemurafenib causes programmed corpuscle afterlife in melanoma corpuscle lines. Vemurafenib interrupts the B-Raf/MEK footfall on the B-Raf/MEK/ERK alleyway − if the B-Raf has the accepted V600E mutation.

Vemurafenib alone works in melanoma patients whose blight has a V600E BRAF alteration (that is, at amino acid position amount 600 on the B-Raf protein, the accustomed valine is replaced by glutamic acid). About 60% of melanomas accept this mutation. It aswell has ability adjoin the rarer BRAF V600K mutation. Melanoma beef after these mutations are not inhibited by vemurafenib; the biologic paradoxically stimulates accustomed BRAF and may advance bump advance in such cases.

Three mechanisms of attrition to vemurafenib (covering 40% of cases) accept been discovered:

Cancer beef activate to overexpress corpuscle apparent protein PDGFRB, creating an another adaptation pathway.

A additional oncogene alleged NRAS mutates, reactivating the accustomed BRAF adaptation pathway.

Stromal corpuscle beard of hepatocyte advance agency (HGF).