HIF1α and HIF2α, through complex mechanisms, synergistically increase IGF1R expression and activate downstream signaling pathways, such as the PI3K/AKT signaling pathway, which promotes tumor cell survival and proliferation, ultimately leading to resistance to temozolomide (TMZ) (Wen et al., 2023; Xiong et al., 2023). Here, EPAS1 is linked to neoplasm.