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) | |