Skip to main content
. 2018 Jun 12;8:202. doi: 10.3389/fonc.2018.00202

Table 1.

Established and potential targets for the treatment of melanoma and their level of action.

Type of target Examples of drugs/agents Comment Selected Reference
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)