Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Table 1 Potential therapeutic targets in melanoma stem/progenitor cells and their progenies

Targeted deregulated element	Name of inhibitory agent
mAb against stem cell-like surface marker
CD133	Anti-CD133 mAb
ABCB5	Anti-ABCB5 mAb
Growth factor signaling inhibitor
EGFR (erbB1) antibody	mAb-C225, cetuximab (IMC-C225), IMC-1121B
EGFR-TKI	Gefitinib, erlotinib, AG1478, PD153035
Anti-EGF antibody	ABX-EGF
Pan-erbB1/erbB2/erbB3/erbB4-TKI	Cl1033
MET	SUI1274
Hedgehog	Anti-SHH antibody, SMO inhibitor (cyclopamine, GDC-0449, BMS-833923, NVP-LDE225, IPI-926 IPI-269609)
Wnt/β-catenin	Anti-Wnt antibody, WIF-1
Notch	γ-secretase inhibitor (DAPT, MK-0752,GSI-18)
Nodal/Cripto	LEFTY, Anti-Cripto mAb
KIT	Imatinib mesylate, dasatinib
HA/CD44	Anti-CD44 mAb, soluble CD44 protein
VEGF	Anti-VEGF antibody (bevacizumab)
VEGFR2	Anti-VEGFR-2 mAb (DC101)
VEGFR2/EGFR/RET	Vandetanib (ZD6474)
VEGFRs, PDGFRs, KIT	Sunitinib
B-Raf, C-Raf, KIT, PDGFRs, VEGFR2 and 3	Sorafenib
ECM component/integrin	Anti-integrin antibody
CXCR4	AMD3100
Intracellular signaling inhibitor
B-RafE600V	PLX 4032, PLX4720
MEK1/2	AZD6244 (ARRY-142886), PD0325901
PI3K	LY294002
mTOR	Rapamycin, CCl-779,
PI3K/mTOR	PI-103
NF-κB	IkBα inhibitor, sulfasalazine, bortezomib (PS-341) salinosporamides A (NPI-0052), parthenolide
COX-2	NS-396, etodolax, celecoxib, rofecoxib
Immunomodulatory agent
Immune and/or vascular systems	Imiquimod, INF-α, IL-2, IL-21, anti-CTLA-4, mAb (ipilimumab “MDX 010”and tremelimumab “CP-675, 206”)

CTLA-4: Cytotoxic T lymphocyte-associated antigen 4; DAPT: N-(N-3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; ECM: Extracellular matrix; EGF: Epidermal growth factor; EGFR: Epidermal growth factor receptor; IκBα: Inhibitor of nuclear factor-κBα; IL: Interleukin; INF: Interferon; mAb: Monoclonal antibody; NF-κB: Nuclear factor-kappaB; PDGFRs: Platelet-derived growth factor receptors; MET: Hepatocyte growth factor receptor; PI3K: Phosphatidylinositol 3’-kinase; SMO: Smoothened; TKI: Tyrosine kinase inhibitor; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; WIF-1: Wingless inhibitory factor-1; Wnt: Wingless ligand.