Frontiers in Endocrinology (Sep 2021)

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

  • Andria Rakotomalala,
  • Andria Rakotomalala,
  • Alexandre Escande,
  • Alexandre Escande,
  • Alexandre Escande,
  • Alessandro Furlan,
  • Alessandro Furlan,
  • Samuel Meignan,
  • Samuel Meignan,
  • Eric Lartigau,
  • Eric Lartigau,
  • Eric Lartigau

DOI
https://doi.org/10.3389/fendo.2021.742215
Journal volume & issue
Vol. 12

Abstract

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Radiotherapy is an important component of cancer treatment, with approximately 50% of all cancer patients receiving radiation therapy during their course of illness. Nevertheless, solid tumors frequently exhibit hypoxic areas, which can hinder therapies efficacy, especially radiotherapy one. Indeed, hypoxia impacts the six parameters governing the radiotherapy response, called the « six Rs of radiation biology » (for Radiosensitivity, Repair, Repopulation, Redistribution, Reoxygenation, and Reactivation of anti-tumor immune response), by inducing pleiotropic cellular adaptions, such as cell metabolism rewiring, epigenetic landscape remodeling, and cell death weakening, with significant clinical repercussions. In this review, according to the six Rs, we detail how hypoxia, and associated mechanisms and pathways, impact the radiotherapy response of solid tumors and the resulting clinical implications. We finally illustrate it in hypoxic endocrine cancers through a focus on anaplastic thyroid carcinomas.

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