PFKFB3 and neoplasm: The field has to balance a difficult bargain between two challenges: first, to bring novel strategies that apparently are more effective than ‘just’ inhibiting VEGF quickly to clinical application, among them combined VEGF and ANG-2 blockade or novel metabolism targeted strategies such as PFKFB3 inhibition; and second, to exclude as best as possible that these interventions produce detrimental unwanted modulations of the tumor and its microenvironment that exhaust the beneficial effects that were pronounced in preclinical studies.