Targeting PIM kinases to oppose hypoxia-mediated therapeutic resistance

PIM kinase family members have been implicated as important factors in the progression and prognosis of various malignancies, including leukemia, breast, and prostate cancer. As a result, PIM kinases are emerging as potential targe ts for solid tumors. In fact, many pharmacological inhibitors of PIM kinases are already under clinical trials [1]. A growing body of evidence suggests that PIM kinases are particularly important in the context of cellular stress, such as hypoxia. Notably, PIM kinase expression is increased in hypoxia in a HIF-1- independent manner, which makes PIM inhibition a novel approach to target the hypoxic tumor microenvironment. Recent reports highlight hypoxia-induced PIM kinase expression as a novel signal transduction pathway that provides protection against hypoxic stress by promoting survival and angiogenesis (Figure (Figure1)1) [2,3]