Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.
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TLDR
In this article, the authors analyzed how the hypoxia-induced cellular responses involving hypoxyia-inducible factor-1, heat-shock transcription factor 1, heat shock proteins, glucose-regulated proteins, epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial-mesenchymal transition and exosome generation contribute to the radioresistance of hypoxic tumors.Abstract:
Within aggressive malignancies, there usually are the “hypoxic zones”—poorly vascularized regions where tumor cells undergo oxygen deficiency through inadequate blood supply. Besides, hypoxia may arise in tumors as a result of antiangiogenic therapy or transarterial embolization. Adapting to hypoxia, tumor cells acquire a hypoxia-resistant phenotype with the characteristic alterations in signaling, gene expression and metabolism. Both the lack of oxygen by itself and the hypoxia-responsive phenotypic modulations render tumor cells more radioresistant, so that hypoxic tumors are a serious challenge for radiotherapy. An understanding of causes of the radioresistance of hypoxic tumors would help to develop novel ways for overcoming this challenge. Molecular targets for and various approaches to radiosensitizing hypoxic tumors are considered in the present review. It is here analyzed how the hypoxia-induced cellular responses involving hypoxia-inducible factor-1, heat shock transcription factor 1, heat shock proteins, glucose-regulated proteins, epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial–mesenchymal transition and exosome generation contribute to the radioresistance of hypoxic tumors or may be inhibited for attenuating this radioresistance. The pretreatments with a multitarget inhibition of the cancer cell adaptation to hypoxia seem to be a promising approach to sensitizing hypoxic carcinomas, gliomas, lymphomas, sarcomas to radiotherapy and, also, liver tumors to radioembolization.read more
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References
More filters
Journal ArticleDOI
New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer
TL;DR: It is highlighted how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state which could function as cancer stem cells, and its effects on the immunobiology of carcinomas.
Journal ArticleDOI
AMPK: guardian of metabolism and mitochondrial homeostasis.
Sébastien Herzig,Reuben J. Shaw +1 more
TL;DR: How AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology is discussed.
Journal ArticleDOI
Revisiting the role of ABC transporters in multidrug-resistant cancer
Robert W. Robey,Kristen M. Pluchino,Matthew D. Hall,Antonio Tito Fojo,Antonio Tito Fojo,Susan E. Bates,Susan E. Bates,Michael M. Gottesman +7 more
TL;DR: Evidence is presented indicating that it is time to revisit the investigation into the role of ABC transporters in efficient drug delivery in various cancer types and at the blood–brain barrier, and push forward their clinical application as biomarkers and as targets in combination therapies in order to improve anticancer drug efficiency.
Journal ArticleDOI
The HSP90 chaperone machinery
TL;DR: Owing to the importance of HSP90 in the regulation of many cellular proteins, it has become a promising drug target for the treatment of several diseases, which include cancer and diseases associated with protein misfolding.
Journal ArticleDOI
Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
TL;DR: A constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit, both spatially and temporally, in the hypoxic environment of tumours.