Cargando…

Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy

Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to...

Descripción completa

Detalles Bibliográficos
Autores principales: Wadden, Jack, Ravi, Karthik, John, Vishal, Babila, Clarissa May, Koschmann, Carl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018987/
https://www.ncbi.nlm.nih.gov/pubmed/35464472
http://dx.doi.org/10.3389/fimmu.2022.882452
_version_ 1784689147239202816
author Wadden, Jack
Ravi, Karthik
John, Vishal
Babila, Clarissa May
Koschmann, Carl
author_facet Wadden, Jack
Ravi, Karthik
John, Vishal
Babila, Clarissa May
Koschmann, Carl
author_sort Wadden, Jack
collection PubMed
description Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to treatment, but is an imperfect tool. Imaging does not provide molecular information, which is becoming critically important for identifying targeted immunotherapies and monitoring tumor evolution. Furthermore, immunotherapy induced inflammation can masquerade as tumor progression in images (pseudoprogression) and confound clinical decision making. More recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for minimally invasive glioma diagnosis and disease monitoring. cf-tDNA is shed by gliomas into surrounding biofluids (e.g. cerebrospinal fluid and plasma) and, if precisely quantified, might provide a quantitative measure of tumor burden to help resolve pseudoprogression. cf-tDNA can also identify tumor genetic mutations to help guide targeted therapies. However, due to low concentrations of cf-tDNA, recovery and analysis remains challenging. Plasma cf-tDNA typically represents <1% of total cf-DNA due to the blood-brain barrier, limiting their usefulness in practice and motivating the development and use of highly sensitive and specific detection methods. This mini review summarizes the current and future trends of various approaches for cf-tDNA detection and analysis, including new methods that promise more rapid, lower-cost, and accessible diagnostics. We also review the most recent clinical case studies for longitudinal disease monitoring and highlight focus areas, such as novel accurate detection methodologies, as critical research priorities to enable translation to clinic.
format Online
Article
Text
id pubmed-9018987
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90189872022-04-21 Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy Wadden, Jack Ravi, Karthik John, Vishal Babila, Clarissa May Koschmann, Carl Front Immunol Immunology Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to treatment, but is an imperfect tool. Imaging does not provide molecular information, which is becoming critically important for identifying targeted immunotherapies and monitoring tumor evolution. Furthermore, immunotherapy induced inflammation can masquerade as tumor progression in images (pseudoprogression) and confound clinical decision making. More recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for minimally invasive glioma diagnosis and disease monitoring. cf-tDNA is shed by gliomas into surrounding biofluids (e.g. cerebrospinal fluid and plasma) and, if precisely quantified, might provide a quantitative measure of tumor burden to help resolve pseudoprogression. cf-tDNA can also identify tumor genetic mutations to help guide targeted therapies. However, due to low concentrations of cf-tDNA, recovery and analysis remains challenging. Plasma cf-tDNA typically represents <1% of total cf-DNA due to the blood-brain barrier, limiting their usefulness in practice and motivating the development and use of highly sensitive and specific detection methods. This mini review summarizes the current and future trends of various approaches for cf-tDNA detection and analysis, including new methods that promise more rapid, lower-cost, and accessible diagnostics. We also review the most recent clinical case studies for longitudinal disease monitoring and highlight focus areas, such as novel accurate detection methodologies, as critical research priorities to enable translation to clinic. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9018987/ /pubmed/35464472 http://dx.doi.org/10.3389/fimmu.2022.882452 Text en Copyright © 2022 Wadden, Ravi, John, Babila and Koschmann 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 Immunology
Wadden, Jack
Ravi, Karthik
John, Vishal
Babila, Clarissa May
Koschmann, Carl
Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title_full Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title_fullStr Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title_full_unstemmed Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title_short Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
title_sort cell-free tumor dna (cf-tdna) liquid biopsy: current methods and use in brain tumor immunotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018987/
https://www.ncbi.nlm.nih.gov/pubmed/35464472
http://dx.doi.org/10.3389/fimmu.2022.882452
work_keys_str_mv AT waddenjack cellfreetumordnacftdnaliquidbiopsycurrentmethodsanduseinbraintumorimmunotherapy
AT ravikarthik cellfreetumordnacftdnaliquidbiopsycurrentmethodsanduseinbraintumorimmunotherapy
AT johnvishal cellfreetumordnacftdnaliquidbiopsycurrentmethodsanduseinbraintumorimmunotherapy
AT babilaclarissamay cellfreetumordnacftdnaliquidbiopsycurrentmethodsanduseinbraintumorimmunotherapy
AT koschmanncarl cellfreetumordnacftdnaliquidbiopsycurrentmethodsanduseinbraintumorimmunotherapy