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Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches

To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treate...

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Autores principales: Ribba, Benjamin, Roller, Andreas, Helms, Hans-Joachim, Stern, Martin, Bleul, Conrad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030934/
https://www.ncbi.nlm.nih.gov/pubmed/36968790
http://dx.doi.org/10.3389/fphar.2022.1058220
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author Ribba, Benjamin
Roller, Andreas
Helms, Hans-Joachim
Stern, Martin
Bleul, Conrad
author_facet Ribba, Benjamin
Roller, Andreas
Helms, Hans-Joachim
Stern, Martin
Bleul, Conrad
author_sort Ribba, Benjamin
collection PubMed
description To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treated with checkpoint inhibitors and targeted therapies. This analysis highlights opportunities for pharmacometrics approaches such as for optimizing sampling design strategies. It also highlights challenges related to the nature of the data and associated variability overall emphasizing the importance of mechanistic modeling studies of the underlying biology of ctDNA processes such as shedding, release and clearance and their relationships with tumor size dynamic and treatment effects.
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spelling pubmed-100309342023-03-23 Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches Ribba, Benjamin Roller, Andreas Helms, Hans-Joachim Stern, Martin Bleul, Conrad Front Pharmacol Pharmacology To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treated with checkpoint inhibitors and targeted therapies. This analysis highlights opportunities for pharmacometrics approaches such as for optimizing sampling design strategies. It also highlights challenges related to the nature of the data and associated variability overall emphasizing the importance of mechanistic modeling studies of the underlying biology of ctDNA processes such as shedding, release and clearance and their relationships with tumor size dynamic and treatment effects. Frontiers Media S.A. 2023-03-08 /pmc/articles/PMC10030934/ /pubmed/36968790 http://dx.doi.org/10.3389/fphar.2022.1058220 Text en Copyright © 2023 Ribba, Roller, Helms, Stern and Bleul. 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 Pharmacology
Ribba, Benjamin
Roller, Andreas
Helms, Hans-Joachim
Stern, Martin
Bleul, Conrad
Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title_full Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title_fullStr Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title_full_unstemmed Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title_short Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
title_sort circulating tumor dna: opportunities and challenges for pharmacometric approaches
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030934/
https://www.ncbi.nlm.nih.gov/pubmed/36968790
http://dx.doi.org/10.3389/fphar.2022.1058220
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