Table 1.
Most significant somatic driver mutations and drugs. In the columns were indicated the gene names, the corresponding mutated proteins and the percentage of the melanoma patients carrying the indicated mutations as well as drugs targeting the mutated proteins, drug approval date, drug targets and some notes.
| Gene | Mutated Protein | Frequency (%) * |
Drug/ First Approval Date |
Target | Note |
|---|---|---|---|---|---|
| B-RAF | V600E V600K V600R | ~60 | Vemurafenib/2011 Dabrafenib/2013 Encorafenib/2018 |
BRAFV600E, V600R, V600K kinases | // |
| N-RAS | Q61K Q61R G12D |
~20 | // | // | Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting upstream/downstream NRAS effectors/regulators are in clinical trials |
| MAP2K1/MAP2K2 | E203K E207K | 8 | Trametinib/2013 Cobimetinib/2014 Binimetinib/2017 |
MEK1/MEK2 kinases MEK1 Kinase MEK1/MEK2 kinases |
AZD8330, TAK-733, GDC-0623 are some of MEK1/2 inhibitors in clinical trials |
| PIK3CA | H1047R E545K | ~5 [12] | // | // | class I PI3K, β-sparing PI3K, PI3Kα inhibitors are in clinical trials |
| RAC1 | P29S | ~4 [13] | Under development [14] |
// | Patients carrying RAC1P29S show an increased expression of PD-L1 [15]. Immunotherapy studies by using anti-PD1 or anti PD-L1 antibodies are ongoing |
* Frequency from the TCGA melanoma cohort.