Activation 0f S-phase genes(Cycle E, A, E2Fs,

DHFR,TK,TS,POL,CDK1)

Active (E2F)

Strategies for signalling inhibition

Tyrosine kinase inhibitors (TKIs)

Immuneeffector cell

Anti-ligand mAbs

BispecificAbs

Anti-receptormAbs

Ligand/toxin conjugate

scFv/toxinconjugates

Ligand-genisteinconjugates

IntracellularscFvs

Nucleus

Antisense

Inhibitors of other signalling molecules

DNA

Mode of action of EGFR inhibitors

Membrane

Extracellular

Intracellular

R

K

R

K EGFR-TKIEGFR-TKI Signalling

Proliferation Cell survival (anti-apoptosis)

Growth factors

Chemotherapy/radiotherapy sensitivity

Angiogenesis

Metastasis

R, epidermal growth factor receptor

EGF/TGFα

Antibody