Established effective targets on plasma membrane |
c-kit |
Imatinib (Glivec, Imatinib) |
In mucosal melanoma |
(50, 146) |
IGF-1 |
Linsitinib |
Phase I i association with Erlotinib |
(147) |
Epidermal growth factor |
Gefitinib (Iressa), Erlotinib (Tarceva) |
Approved for lung cancer, studied on melanoma, both cutaneous and uveal |
(148, 149) |
|
Potential effective targets on plasma membrane |
GNAQ/GNA11 |
PKC inhibitor AEB071 (sotrastaurin) |
In uveal melanoma |
(150) |
|
Established effective targets within signaling transduction pathways |
BRAF |
Vemurafenib, dabrafenid, encorafenib |
In skin, melanoma binds to and inhibits activated BRAF |
(47, 48) |
MEK |
Trametinib, cobimetinib, binimetinib |
Often associated with BRAF inhibitors to overcome acquired resistance |
(49) |
|
Potential effective targets within signaling transduction pathways |
NRAS |
Farnesyltransferaze inhibitors (R115777) |
Most frequently mutated at hotspots in exon 1 (codon 12) and exon 2 (codon 61), which results in the prolongation of its active GTP-bound state |
(91, 151) |
PI3K |
Pictilisib |
In melanomas with PTEN aberrations |
(96) |
ALK |
Crizotinib |
In uveal and spitzoid melanoma |
(152) |
CDK4/6 |
Abemaciclib, palbociclib |
In melanomas with CDKN2A aberrations |
(99, 100) |
|
Established effective nuclear targets |
None described so far |
|
Potential effective nuclear targets |
MITF |
CH5552074 |
Inhibition of cell growth by reducing the expression level of MITF protein |
(153) |
TERT |
In vitro test with Telomerase inhibitor IX |
Acral and cutaneous melanoma |
(154) |
BAP1 |
In vitro with ubiquitin vinyl sulfone (Ub-VS) |
In uveal melanoma |
(105) |
Histone deacetylases |
Entinostat |
In association with pembrolizumab in melanoma |
(109) |
(159) |
|
Established effective immune targets |
CTLA-4 |
Ipilimumab |
T-cell activator and blocks B7-1 and B7-2 T-cell co-stimulatory pathways |
(155) |
PD-1 |
Pembrolizumab, nivolumab |
Binds to PD-1 and as such activates T-cell-mediated immune responses |
(57, 58) |
PDL-1 |
Atezolizumab |
|
(156) |
IDO |
Epacadostat |
|
(157) |
|
Potential effective immune targets |
SD-101 |
|
Via the toll-like receptor 9 |
(127) |
OX40 |
|
Co-stimulatory molecule that can be expressed by activated immune cells |
(127) |
CD137 |
|
Member of the TNFR super family |
(127, 158) |
GITR |
|
Glucocorticoid induced TNF receptor |
(127) |