TY - JOUR
T1 - Hypoxia-driven effects in cancer
T2 - Characterization, mechanisms, and therapeutic implications
AU - Shi, Rachel
AU - Liao, Chengheng
AU - Zhang, Qing
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3
Y1 - 2021/3
N2 - Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferat-ing and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochon-drial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.
AB - Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferat-ing and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochon-drial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.
KW - Chemoresistance
KW - Hypoxia
KW - Hypoxia-inducible factors
KW - Metastasis
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U2 - 10.3390/cells10030678
DO - 10.3390/cells10030678
M3 - Review article
C2 - 33808542
AN - SCOPUS:85103862365
SN - 2073-4409
VL - 10
SP - 1
EP - 26
JO - Cells
JF - Cells
IS - 3
M1 - 678
ER -