HIF1A and neoplasm: Several extrinsic and intrinsic cues, including oncogene activation, growth factors, hypoxia, cytokines, pH, and free radicals were shown to induce major pro-survival pathways, including the ERK/MAPK, JAK/STAT and PI3K/AKT/mTOR cascades, in turn regulating both HIF-1α gene expression and protein translation, hence promoting tumor progression, invasion and therapeutic resistance [157,158].