Table 1.

Major differences between monoclonal antibodies and small molecule tyrosine kinase inhibitors.

	mAb	Small molecule TKI
Administration	Intravenous	Oral or parenteral
Target availability	Must be extracellular	Extra/intra-cellular
Cost	US$ 4,200/month (trastuzumab)	US $1,800/month (gefitinib)
Size	~150,000 daltons	~400 daltons
Diffusion	Near vessels, surrounding tumor area; inefficient delivery	Easy to diffuse, translocate though plasma membranes, may reach brain tissues
Toxicity	Low toxicity	Mid-high toxicity
Half-Life	Days-weeks	<72 h
Mechanism of Action	Disrupt ligand-receptor or receptor-receptor (homo/hetrodimerization) interactions, receptor downregulation, induction of apoptosis	Bind to target kinase(s), inhibit phosphorylation and downstream signaling pathways. Induce apoptosis.
Approval success rate	18-24%	5%
Mechanisms of resistance	Protein Modifications: Switch of surface receptors. Shedding of the extracellular portion of the receptor. Expression of truncated receptors. Modification of receptor structure. Activation of downstream signaling pathways.	Genetic modifications: Point Mutations (Activating mutations). Amplifications (Target gene). Deletions. Protein Modifications: Overexpression of the target protein. Activation of alternative pathways. Overexpression of Multidrug resistance genes.