Targeting the BMK1 MAP Kinase Pathway in Cancer Therapy

The big mitogen-activated protein kinase 1 (BMK1) pathway is the most recently discovered and least-studied mammalian mitogen-activated protein (MAP) kinase cascade, ubiquitously expressed in all types of cancer cells tested so far. Mitogens and oncogenic signals strongly activate this cellular MAP kinase pathway, thereby passing down proliferative, survival, chemo-resistance, invasive and angiogenic signals in tumor cells. Recently, several pharmacological small molecule inhibitors of this pathway have been developed. Among them, BMK1 inhibitor, XMD8-92, blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals. On the other hand, MEK5 inhibitors, BIX02188, BIX02189 and compound 6, suppress cellular MEK5 activity but no data yet on their effectiveness in animal.