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Onkologie 14. April 2010

Fibroblast growth factor receptors (FGFR) as possible therapeutic targets in human non-small cell lung cancer

The fibroblast growth factors (FGFs) are a large family of peptide growth factors playing essential roles in embryonic development, tissue maintenance and wound healing. FGFs interact with target cells by binding to four high-affinity receptor tyrosine kinases (RTK) termed FGFR1-4. Based on the proliferative and anti-apoptotic as well as pro-angiogenic functions of the FGF/FGFR signal module, it is not surprising that deregulations occur at multiple levels in many types of human cancer. Recently, it got obvious that FGF/FGFR signals might also be hyperactivated in non-small cell lung cancer (NSCLC) by diverse molecular mechanisms leading to autocrine support of tumour cell proliferation, migration and survival as well as paracrine activities including neo-angiogenesis. Additionally, FGF/FGFR signals turned out to be involved in therapy resistance against not only classical chemotherapy but also novel targeted anti-NSCLC agents like inhibitors of the epidermal growth factor receptor (EGFR). This suggests that FGF/FGFR inhibitors might represent a novel component for combined NSCLC therapy approaches.

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