Tyrosine kinase inhibitors and gemcitabine: New treatment options in pancreatic cancer?

Gemcitabine (2′,2′-difluoro-2′-deoxycytidine), a pyrimidine analog with a broad-spectrum of antitumor activity.

Two methods of blocking tyrosine kinase-dependent growth factor signaling are shown. (1) Inhibition of receptor–ligand interaction by receptor specific monoclonal antibodies (MABs); (2) inhibition of intracellular tyrosine kinase activity by small-molecule tyrosine kinase inhibitors (TKIs). RTK: receptor tyrosine kinase (growth factor receptor); CTK: cytoplasmic tyrosine kinase (intracellular signaling protein).

EGF-receptor binding leads to tyrosine kinase phosphorylation and downstream activation of different signal processing pathways including PI3-kinase and MAP-kinase pathways. Subsequent effects on gene transcription result in transformation of the tumor cell, promoting survival, proliferation, migration and other tumor-specific actions.