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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...

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Autores principales: Lüke, Florian, Harrer, Dennis Christoph, Pantziarka, Pan, Pukrop, Tobias, Ghibelli, Lina, Gerner, Christopher, Reichle, Albrecht, Heudobler, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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