Combined inhibition of PIM and VEGF produced a synergistic antitumor response characterized by decreased proliferation, reduced tumor vasculature, and decreased metastasis.<b>Conclusions:</b> This study describes PIM kinase expression as a novel mechanism of resistance to antiangiogenic agents.
Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis.
PIM1 is overexpressed in human cancer diseases and has been associated with metastasis and overall treatment response; in experimental models, inhibition of PIM1 suppressed cell proliferation and migration, induced apoptotic cell death and synergized with other chemotherapeutic agents.
However, when samples of primary tumor and metastasis retrieved from the same patients (n=26) were analyzed, nearly significant correlation of Pim-1 expression with histological grade was found (p=0.06).