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

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Axel KleespiesChristiane J Bruns

Abstract

Pancreatic cancer (PCa) is one of the most lethal malignancies in humans. Gemcitabine is the current standard chemotherapy of advanced PCa but it is still far from optimal and novel therapeutic strategies are urgently needed. For the near future, tyrosine kinase inhibitors (TKIs) hold great promise as a therapeutic strategy. Tyrosine kinases (TKs) play a pivotal role in intercellular signal transduction and regulate crucial processes of tumor cells such as proliferation, migration, survival and angiogenesis. Several TKs--such as EGFR, VEGFR, PDGFR and Src--are known to be overexpressed or constitutively activated in PCa. Hence, blocking receptor tyrosine kinases (RTKs) and non-receptor, cytoplasmic tyrosine kinases (CTKs) represents a rational approach to treat PCa. In particular, cetuximab and erlotinib, the monoclonal antibodies against EGFR-1 (ErbB-1) showed promising activity in Phase II and Phase III trials and their combination with gemcitabine resulted in synergistic antitumor activity. In addition, small antiangiogenic molecules such as VEGFR-2 inhibitors, PDGFR inhibitors and multiple receptor targeting agents are under active investigation. Association of chemoresistance with the activity of certain tyrosine kinases (...Continue Reading

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