Conversely, HIF2α can bind and stabilize the MYC:MAX heterodimer, promoting MYC-induced transcriptional changes.43 This is more likely to be of importance in the hypoxia-induced metabolic transformation in non-MYC-amplified tumours, as the HIFα can be outcompeted in tumours with high levels of MYC expression for the MAX subunit.44 The stabilization of HIF1, HIF2 and p53 and the expression of MYC therefore combine to form a graded response to changes in oxygen tension with different players influencing metabolism as the degree of hypoxia increases (Figure 1). This evidence concerns the gene EPAS1 and neoplasm.