. Author manuscript; available in PMC: 2017 Oct 30.

Published in final edited form as: Curr Oncol Rep. 2008 Sep;10(5):439–446. doi: 10.1007/s11912-008-0067-y

Table 2.

Select combination therapies targeting different components of the melanoma tumor microenvironment in clinical trials

Drug combination	Mechanism	Phase	Comments
Bevacizumab and BAY 43-9006	Anti-VEGF antibody; multikinase inhibitor	1/2	Response to MTD evaluated by biochemical changes in Ras-Raf-MAPK and VEGF signaling in tumor lysates by microarray and proteomics
PTK787 (valatanib) and Rad-001	Binds to and inhibits the protein kinase domain of VEGFR; rapamycin analogue and mTOR inhibitor	1	Binds to and inhibits PDGFR, c-Kit, and c-Fms
BAY 43-9006 and CCI-779 or R115777	Multikinase inhibitor; mTOR inhibitor; farnesyltransferase inhibitor	2	Inhibits c-Raf, PDGF, VEGR, c-Kit; an ester analogue of rapamycin
Vorinostat and FR901228 (romidepsin)	Histone deacetylase inhibitors	2	Proapoptotic in preclinical studies; FR901228 blocks hypoxia-induced angiogenesis and depletes several Hsp90-dependent oncoproteins
NP10052 and vorinostat	Proteosome inhibitor; histone deacetylase inhibitor	1	Enhanced potency in preclinical models
Bortezomib, paclitaxel, and carboplatin	Reversibly inhibits the 26S proteosome; mitotic inhibitor; DNA alkylating agent	2	Chemosensitization/potentiation therapy
MEDI-522 with or without dacarbazine	Monoclonal antibody anti-α_vβ₃ integrin; alkylating agent	2	Combination is well tolerated; preliminary overall survival results suggest potential clinical activity
Volociximab and dacarbazine	Anti-α₅β₁ integrin antibody; alkylating agent	2	Study has been completed
PS-341 and temozolomide	Proteosome inhibitor; alkylating agent	2

Hsp—heat shock protein; MAPK—mitogen-activated protein kinase; MTD—maximum tolerated dose; mTOR—mammalian target of rapamycin; PDGFR—platelet-derived growth factor receptor; VEGFR—vascular endothelial growth factor receptor.