Hif-Prolyl Hydroxylase Domain Proteins (Phds) in Cancer – Potential Targets for Anti-Tumor Therapy?

• DOI: 10.20944/preprints202012.0553.v1
• Publication Date: 2020-12-23T08:17:08Z
• Authors: Diana Gaete; Diego Rodriguez; Deepika Watts; Sundary Sormendi; Triantafyllos Cha...; Ben Wielockx
• Keywords: Hypoxia; Hypoxia-Inducible Factors

Solid tumors are typically associated with unbridled proliferation of malignant cells, accompanied by an immature and dysfunctional tumor-associated vascular network. Consequent impairment in transport nutrients oxygen eventually leads to a hypoxic environment wherein cells must adapt survive overcome these stresses. Hypoxia inducible factors (HIFs) central transcription the hypoxia response drive expression vast number survival genes cancer tumor microenvironment. HIFs tightly controlled class sensors, HIF-prolyl hydroxylase domain proteins (PHDs), which hydroxylate HIFs, thereby marking them for proteasomal degradation. Remarkable intense research during past decade has revealed that, contrary expectations, PHDs often overexpressed many types that inhibition can lead decreased growth, impaired metastasis diminished immune-tolerance. Therefore, represent attractive therapeutic target research. Multiple PHD inhibitors have been developed either recently accepted China as erythropoiesis stimulating agents (ESA) or currently phase III trials. We review here function related opportunities.