Table 3.

Examples of current and future treatments for metastatic disease

Cellular functions	Examples of molecular targets	Examples of therapeutic agents in clinical or preclinical development
DNA replication	DNA, telomerase	Radiotherapy, alkylating agents, platinum drugs
DNA repair	Topoisomerases , PARP	Antimetabolites
Cell cycle	Tubulin, cyclins, aurora kinases	Anthracyclines, taxanes, VX-680
Metabolism, protein synthesis	RNA, thymidylate synthase	Antifolates, antimetabolites, tomudex, OSI-7904L
Oncogenic signalling	EGFR, ERB-B2, BCR-ABL, KIT, RET, PDGFR, mTOR, PI3K, RAF, COX2, PKC, farnesyl transferase, HSP90 chaperone, proteasome	Gefitinib, erlotinib, cetuximab, trastuzumab, imatinib, vandetanib [A1], RAD001, PI103, celecoxib, 17AAG, 17DMAG, bortezomib
Endocrine signalling	ER, aromatase, AR, CYP450c17	Tamoxifen, anastrozole, flutamide, abiraterone (Cougar Biotechnology)
Angiogenesis	VEGF, VEGF-R, integrins	Bevacizumab, semaxanib, vatalanib [A1], vitaxin [A1], combretastatins, endostatin, angiostatin
Proteolysis/invasion	uPA, matrix metalloproteinases	Amiloride, marimastat, prinomastat [A1], BMS-275291
Osteolysis	Farnesyle diphosphate synthase	Bisphosphonates (pamidronate, clodronate, zoledronate)
Drug-resistant phenotypes	BCR-ABL and EGFR mutations	Dasatinib, bosutinib (SKI-606, Wyeth)
Cell motility	C-MET, Src, ROCK, PLCγ, SDF1-CXCR4	PHA665752, AMD3100
Tumour-host interactions	TGFβ, Slit-Robo, Eph-Ephrins, angiopoietins-Tie
Osteoclastogenesis	RANKL, endothelin receptor	Denosumab (AMG162, Amgen)
Lymphangiogenesis	VEGFR-3	PTK/ZK
Hypoxia/glycolysis	HIF1α, NFκB, LOX	YC-1, vitexin [A1]
Epigenetic events	Acetylation, methylation	SAHA, LAQ824
Stem cells	Notch, Hedgehog, Wnt signalling pathways	Cyclopamine
Anoikis/survival	TRKB, PI3K, AKT; Twist, Snail, Bmi-1 transcription factors	CEP751, PI103, ZSTK474