Table 1.
Clinical trials and other studies on applying senotherapeutics to melanoma. HSP: heat shock protein; Bcl-2/Bcl-xL: B-cell lymphoma 2/B-cell lymphoma extra-large; HDAC: histone deacetylase; OXR1: oxidation resistance 1; BET: bromodomain and extraterminal domain; PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; mTOR: mammalian target of rapamycin; MIC: melanoma initiating cells This table is not an all-inclusive list of studies with senotherapeutics for melanoma, and a more extensive list of senotherapeutics used in additional cancers can be found in Prasanna, et al. [145].
| Drug | Mechanisms of Action | Treatment | Developmental Stage |
|---|---|---|---|
| Alvespimycin | HSP inhibitor | Alvespimycin hydrochloride |
Clinical Trail: Phase 1; NCT00089362; Metastatic or unresectable solid tumors including melanoma |
| Alvespimycin hydrochloride | Phase 1; NCT00248521; Adult solid tumor including melanoma [146] | ||
| Alvespimycin hydrochloride |
Discovery Phase: human melanoma cell line [147] |
||
| Tanespimycin | HSP inhibitor | Tanespimycin |
Clinical Trail: Phase 2; NCT00087386; Recurrent or phase III, IV melanoma |
| Tanespimycin | Phase 1; NCT00004065; Refractory advanced solid tumors including melanoma or hematologic cancer | ||
| Tanespimycin | Phase 2; NCT00104897; Metastatic malignant melanoma [148] | ||
| Tanespimycin | Phase 2; Metastatic Melanoma [149] | ||
| Tanespimycin and Sorafenib | Phase 1; Melanoma, renal cancer and colorectal cancer [150] | ||
| Digoxin | Na+/K+ ATPase inhibitor |
Trametinib and Digoxin |
Clinical Trail: Phase 1; NCT02138292; Unresectable or metastatic BRAF wild-type melanoma [151] |
| Vemurafenib and Digoxin | Phase 1; NCT01765569; Advanced BRAFV600 mutant melanoma | ||
| Navitoclax (ABT-263) |
Bcl-2/Bcl-xL inhibitor | Dabrafenib, trametinib, and navitoclax |
Clinical Trail: Phase 1/2; NCT01989585; BRAF mutant melanoma or unresectable or metastatic solid tumors |
| Novitoclax and selumetinib |
Discovery Phase: Melanoma cell lines [152] |
||
| Dasatinib | Pan receptor tyrosine kinase inhibitor |
Dasatinib |
Clinical Trail: Phase 2; NCT00700882; Melanoma (Skin) [153] |
| Dendritic cell Vaccines + Dasatinib | Phase 2; NCT01876212; Metastatic melanoma | ||
| Dasatinib and Dacarbazine | Phase 1/2; NCT00597038; Metastatic Melanoma | ||
| Dasatinib | Phase 2; NCT00436605; Unresectable stage III melanoma or stage IV melanoma | ||
| Dasatinib | Phase 1; Advanced melanoma [154] | ||
| Dasatinib and Dacarbazine | Phase 1; Metastatic melanoma [155] | ||
| Dasatinib |
Discovery Phase: Melanoma cell lines [67] |
||
| Panobinostat (LBH589) | Pan HDAC inhibitor | Panobinostat |
Clinical Trail: Phase 1; NCT01065467; Metastatic Melanoma |
| Panobinostat and Ipilimumab | Phase 1; NCT02032810; Unresectable stage III/IV melanoma | ||
| Temozolomide, Decitabine, Panobinostat | Phase 1/2; NCT00925132; Metastatic Melanoma [156] | ||
| Panobinostat (LBH589) | Phase 1; metastatic melanoma [157] | ||
| Curcumin analog, EF24 | Promote degradation of anti-apoptotic Bcl-2 proteins | EF24 |
Discovery Phase: Malignant melanoma cell lines [158] |
| Piperlongumine | Targets OXR1 | Piperlongumine |
Discovery Phase: Human melanoma cell [143] |
| Ouabain | Na+/K+ ATPase inhibitor |
Ouabain |
Discovery Phase: Malignant melanoma cell lines [159,160] |
| ABT-737 | Bcl-2/Bcl-xL inhibitor | ABT-737 and PLX4720 |
Discovery Phase: Human melanoma cell lines and primary melanoma cell culture [161] |
| ABT-737 and GSI (γ-Secretase Inhibitor) | Non-MIC (bulk of melanoma) and MICs [162] | ||
| JQ1 | BET inhibitor | JQ1 and vemurafenib |
Discovery Phase: BRAF mutant vemurafenib-resistant melanoma cells [163] |
| Quercetin | Activates estrogen receptors and inhibits PI3 kinase | Quercetin |
Discovery Phase: Melanoma cell lines [140,141,142,164,165] |
| Fisetin | Blocks PI3K/AKT/mTOR pathway | Fisetin |
Discovery Phase: Melanoma cell lines [137,138,166,167,168] |