PFKM and cancer: Although the relative roles of PFKFB3 and PFKFB4 are poorly understood, PFKFB4 appears to be essential for cancer cell survival and to correlate highly with hypoxic regions of tumors [16] whereas PFKFB3 localizes to both the cytoplasm and the nucleus where it activates PFK-1 and cyclin dependent kinase 1 respectively [20, 21].