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Drug Repurposing by Tumor Tissue Editing
The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active dr...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270020/ https://www.ncbi.nlm.nih.gov/pubmed/35814409 http://dx.doi.org/10.3389/fonc.2022.900985 |
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author | Lüke, Florian Harrer, Dennis Christoph Pantziarka, Pan Pukrop, Tobias Ghibelli, Lina Gerner, Christopher Reichle, Albrecht Heudobler, Daniel |
author_facet | Lüke, Florian Harrer, Dennis Christoph Pantziarka, Pan Pukrop, Tobias Ghibelli, Lina Gerner, Christopher Reichle, Albrecht Heudobler, Daniel |
author_sort | Lüke, Florian |
collection | PubMed |
description | The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active drugs are considered as a therapeutic aim, e.g., differentiation, transdifferentiation induction, reconstitution of immunosurveillance, the use of alternative cell death mechanisms. Editing of the tumor tissue establishes new biological ‘hallmarks’ as a ‘pressure point’ to attenuate tumor growth. This may be achieved with repurposed, regulatorily active drug combinations, often simultaneously targeting different cell compartments of the tumor tissue. Moreover, tissue editing is paralleled by decisive functional changes in tumor tissues providing novel patterns of target sites for approved drugs. Thus, agents with poor activity in non-edited tissue may reveal new clinically meaningful outcomes. For tissue editing and targeting edited tissue novel requirements concerning drug selection and administration can be summarized according to available clinical and pre-clinical data. Monoactivity is no pre-requisite, but combinatory bio-regulatory activity. The regulatorily active dose may be far below the maximum tolerable dose, and besides inhibitory active drugs stimulatory drug activities may be integrated. Metronomic scheduling often seems to be of advantage. Novel preclinical approaches like functional assays testing drug combinations in tumor tissue are needed to select potential drugs for repurposing. The two-step drug repurposing procedure, namely establishing novel functional systems states in tumor tissues and consecutively providing novel target sites for approved drugs, facilitates the systematic identification of drug activities outside the scope of any original clinical drug approvals. |
format | Online Article Text |
id | pubmed-9270020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92700202022-07-09 Drug Repurposing by Tumor Tissue Editing Lüke, Florian Harrer, Dennis Christoph Pantziarka, Pan Pukrop, Tobias Ghibelli, Lina Gerner, Christopher Reichle, Albrecht Heudobler, Daniel Front Oncol Oncology The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active drugs are considered as a therapeutic aim, e.g., differentiation, transdifferentiation induction, reconstitution of immunosurveillance, the use of alternative cell death mechanisms. Editing of the tumor tissue establishes new biological ‘hallmarks’ as a ‘pressure point’ to attenuate tumor growth. This may be achieved with repurposed, regulatorily active drug combinations, often simultaneously targeting different cell compartments of the tumor tissue. Moreover, tissue editing is paralleled by decisive functional changes in tumor tissues providing novel patterns of target sites for approved drugs. Thus, agents with poor activity in non-edited tissue may reveal new clinically meaningful outcomes. For tissue editing and targeting edited tissue novel requirements concerning drug selection and administration can be summarized according to available clinical and pre-clinical data. Monoactivity is no pre-requisite, but combinatory bio-regulatory activity. The regulatorily active dose may be far below the maximum tolerable dose, and besides inhibitory active drugs stimulatory drug activities may be integrated. Metronomic scheduling often seems to be of advantage. Novel preclinical approaches like functional assays testing drug combinations in tumor tissue are needed to select potential drugs for repurposing. The two-step drug repurposing procedure, namely establishing novel functional systems states in tumor tissues and consecutively providing novel target sites for approved drugs, facilitates the systematic identification of drug activities outside the scope of any original clinical drug approvals. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9270020/ /pubmed/35814409 http://dx.doi.org/10.3389/fonc.2022.900985 Text en Copyright © 2022 Lüke, Harrer, Pantziarka, Pukrop, Ghibelli, Gerner, Reichle and Heudobler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Lüke, Florian Harrer, Dennis Christoph Pantziarka, Pan Pukrop, Tobias Ghibelli, Lina Gerner, Christopher Reichle, Albrecht Heudobler, Daniel Drug Repurposing by Tumor Tissue Editing |
title | Drug Repurposing by Tumor Tissue Editing |
title_full | Drug Repurposing by Tumor Tissue Editing |
title_fullStr | Drug Repurposing by Tumor Tissue Editing |
title_full_unstemmed | Drug Repurposing by Tumor Tissue Editing |
title_short | Drug Repurposing by Tumor Tissue Editing |
title_sort | drug repurposing by tumor tissue editing |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270020/ https://www.ncbi.nlm.nih.gov/pubmed/35814409 http://dx.doi.org/10.3389/fonc.2022.900985 |
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