Cargando…

Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?

Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy...

Descripción completa

Detalles Bibliográficos
Autores principales: Apilan, Alyssa Gabrielle, Mothersill, Carmel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395506/
https://www.ncbi.nlm.nih.gov/pubmed/34445354
http://dx.doi.org/10.3390/ijms22168651
_version_ 1783744188891791360
author Apilan, Alyssa Gabrielle
Mothersill, Carmel
author_facet Apilan, Alyssa Gabrielle
Mothersill, Carmel
author_sort Apilan, Alyssa Gabrielle
collection PubMed
description Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.
format Online
Article
Text
id pubmed-8395506
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83955062021-08-28 Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment? Apilan, Alyssa Gabrielle Mothersill, Carmel Int J Mol Sci Review Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues. MDPI 2021-08-11 /pmc/articles/PMC8395506/ /pubmed/34445354 http://dx.doi.org/10.3390/ijms22168651 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Apilan, Alyssa Gabrielle
Mothersill, Carmel
Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title_full Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title_fullStr Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title_full_unstemmed Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title_short Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
title_sort targeted and non-targeted mechanisms for killing hypoxic tumour cells—are there new avenues for treatment?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395506/
https://www.ncbi.nlm.nih.gov/pubmed/34445354
http://dx.doi.org/10.3390/ijms22168651
work_keys_str_mv AT apilanalyssagabrielle targetedandnontargetedmechanismsforkillinghypoxictumourcellsaretherenewavenuesfortreatment
AT mothersillcarmel targetedandnontargetedmechanismsforkillinghypoxictumourcellsaretherenewavenuesfortreatment