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The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance

1
Cancer Biology & Epigenetics Group—Research Center at Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal
2
Department of Pathology at Portuguese Oncology Institute of Porto (CI-IPOP), Portugal, 4200-072 Porto, Portugal
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Department of Pathology and Molecular Immunology at Institute of Biomedical Sciences Abel Salazar—University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
4
Medical Physics, Radiobiology and Radiation Protection Group—Research Center at Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Genes 2019, 10(11), 927; https://doi.org/10.3390/genes10110927
Received: 7 October 2019 / Revised: 1 November 2019 / Accepted: 12 November 2019 / Published: 14 November 2019
(This article belongs to the Special Issue DNA Damage and Repair after Radiation)
Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15–20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumors, including EC. Accordingly, HIF-1α, involved in cell cycle deregulation, apoptosis, angiogenesis induction and proliferation in cancer, constitutes a predictive marker of resistance to radiotherapy (RT). Deregulation of epigenetic mechanisms, including aberrant DNA methylation and histone modifications, have emerged as critical factors in cancer development and progression. Recently, interactions between epigenetic enzymes and HIF-1α transcription factors have been reported. Thus, further insight into hypoxia-induced epigenetic alterations in EC may allow the identification of novel therapeutic targets and predictive biomarkers, impacting on patient survival and quality of life. View Full-Text
Keywords: Epigenetic; esophageal cancer; hypoxia; microenvironment; radiobiology; radioresistance Epigenetic; esophageal cancer; hypoxia; microenvironment; radiobiology; radioresistance
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Macedo-Silva, C.; Miranda-Gonçalves, V.; Henrique, R.; Jerónimo, C.; Bravo, I. The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance. Genes 2019, 10, 927.

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