NFE2L2 and neoplasm: In addition, given the interplay between HIPK2 with HIF-1α [85,136], HIPK2 and NRF2 [42,44], and NRF2 and HIF-1, it can be speculated that HIPK2 apoptotic activity might be restrained by the HIF-1/NRF2 interplay; therefore, targeting either HIF-1- or NRF2-induced pathways or both is a possible strategy to control tumor progression, in part through reestablishing HIPK2 oncosuppressor activities.