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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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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. |
format | Online Article Text |
id | pubmed-10030934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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