Biology-driven cancer drug development: back to the future

Table 1 Some examples of targeted therapies for cancer

Drug	Brand name	Drug target*	Cancer types
In clinical use
Bevacizumab	Avastin	VEGF	Colorectal, non-small cell lung, breast, renal
Bortezomib	Velcade	Proteasome	Myeloma, lymphoma
Celecoxib	Onsenal	COX2	Familial adenomatous polyposis
Erlotinib	Tarceva
Gefitinib	Iressa	EGFR	Non-small cell, lung, colorectal, head and neck
Cetuximab	Erbitux
Panitumumab	Vectibix
Imatinib	Gleevec
Dasatinib	Sprycel	BCR-ABL, cKIT, PDGFR	Leukemia, gastrointestinal
Nilotinib	Tasigna
Methotrexate		DHFR	Multiple cancer types
RAD001	Certican	mTOR	Renal
Temirolimus	Toricel
Sorafenib	Nexavar	VEGFR, RAF, cKIT, PDGFR	Renal, hepatic
Sunitinib	Sutent
Topotecan	Hycamtin	Topoisomerase I	Multiple cancer types
Irinotecan	Camptosar
Trastuzumab	Herceptin	ERBB2	Breast
Lapatinib	Tykerb	HER2, EGFR	Breast
Tamoxifen	Nolvadex	ERα	Breast
Exemestane	Aromasin
Anastrozole	Arimidex	Aromatase cytochrome P450	Breast
Letrozole	Femara
Rituximab	MabThera	CD20	Lymphoma
Tositumomab	Bexxar
In development
17AAG		HSP90
ABT-737, ABT-263, Obatoclax		BCL-XL, BCL-2
Alvocidib		CDKs
Olaparib, AG014699		PARP1/2
BEZ235		PI3K
GRN163L		hTERT
Mapatumumab		TRAIL Receptor
Nutlin-3		MDM2
PLX4032		BRAF
GDC-0449		SMO
PF-0477736		CHK1

*Target abbreviations: BCL-2, anti-apoptotic protein BCL-2; BCL-XL, anti-apoptotic protein BCL extra large; BCR-ABL, fusion protein of breakpoint cluster region and tyrosine kinase ABL1; BRAF, protein tyrosine kinase BRAF; CD20, B-cell phosphoprotein CD20; CDKs, cyclin-dependent kinases; CHK1, serine/threonine kinase CHK1; cKIT, tyrosine kinase c-KIT; COX2, cyclooxygenase 2; DHFR, dihydrofolate reductase; EGFR, epidermal growth factor receptor; ERα, estrogen receptor α; HER2, human epidermal growth factor receptor 2; HSP90, heat shock protein 90; hTERT, telomerase reverse transcriptase; MDM2, murine double minute 2; mTOR, mammalian target of rapamycin; PARP1/2, poly(ADP-ribose) polymerase 1/2; PDGFR, platelet-derived growth factor receptor; PI3K, phosphatidylinositol 3-kinase; RAF, small GTPase RAF; SMO, Smoothened; TRAIL receptor, TNF-related apoptosis-inducing ligand receptor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.