Tyrosine kinase receptors have important signaling functions in various physiological and pathological pathways. The recognition of their involvement in
tumor angiogenesis, which is the main event of
tumor progression, opened a new era in the discovery of anticancer drugs. Developers soon grasped that by targeting several
tyrosine kinase receptors at once, so-called multitarget
tyrosine kinase inhibitors, a
drug could dramatically affect the progression of
cancer and decrease resistance. Several antiangiogenic, multitarget
tyrosine kinase inhibitors, such as
sorafenib and
sunitinib, are already marketed, while many more are undergoing clinical trials for a range of
cancer types. Boehringer Ingelheim Corp is developing intedanib (BIBF-1120), a triple
kinase inhibitor blocking VEGFR, PDGFR and FGFR for the treatment of several
malignancies and
idiopathic pulmonary fibrosis. The preliminary data for intedanib appears at least as good as that for other antiangiogenic
tyrosine kinase inhibitors or other antiangiogenic approaches that are not targeting the
tyrosine kinases. The sustained inhibition of VEGFR phosphorylation (> 24 h), the fast in vivo clearance and clinical efficacy against a broad range of
malignancies appear to be the major advantages of intedanib. Furthermore, the existing data suggest an excellent safety profile. At the time of publication, intedanib had reached phase III trials for the treatment of NSCLC and
ovarian cancer.