AUTHOR=Tímár József , Sebestyén Anna , Kopper László , Dankó Titanilla TITLE=Hypoxia Signaling in Cancer: From Basics to Clinical Practice JOURNAL=Pathology and Oncology Research VOLUME=27 YEAR=2021 URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609802 DOI=10.3389/pore.2021.1609802 ISSN=1532-2807 ABSTRACT=

Cancer hypoxia, recognized as one of the most important hallmarks of cancer, affects gene expression, metabolism and ultimately tumor biology-related processes. Major causes of cancer hypoxia are deficient or inappropriate vascularization and systemic hypoxia of the patient (frequently induced by anemia), leading to a unique form of genetic reprogramming by hypoxia induced transcription factors (HIF). However, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling independently of oxygen supply. The consequences of HIF activation in tumors are the angiogenic phenotype, a novel metabolic profile and the immunosuppressive microenvironment. Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance. Accordingly, it seems inevitable to combine various therapeutic modalities of cancer patients by existing anti-hypoxic agents such as anti-angiogenics, anti-anemia therapies or specific signaling pathway inhibitors. It is evident that there is an unmet need in cancer patients to develop targeted therapies of hypoxia to improve efficacies of various anti-cancer therapeutic modalities. The case has been opened recently due to the approval of the first-in-class HIF2α inhibitor.