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Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells
A critical barrier to effective cancer therapy is the improvement of drug selectivity, toxicity, and reduced recurrence of tumors expanded from tumor‐initiating stem‐like cells (TICs). The aim is to identify circulating tumor cell (CTC)‐biomarkers and to identify an effective combination of TIC‐spec...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10190641/ https://www.ncbi.nlm.nih.gov/pubmed/36949364 http://dx.doi.org/10.1002/advs.202206812 |
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author | Chen, Chia‐Lin Hernandez, Juan Carlos Uthaya Kumar, Dinesh Babu Machida, Tatsuya Tahara, Stanley M. El‐Khoueiry, Anthony Li, Meng Punj, Vasu Swaminathan, Suresh Kumar Kirtane, Ameya Chen, Yibu Panyam, Jayanth Machida, Keigo |
author_facet | Chen, Chia‐Lin Hernandez, Juan Carlos Uthaya Kumar, Dinesh Babu Machida, Tatsuya Tahara, Stanley M. El‐Khoueiry, Anthony Li, Meng Punj, Vasu Swaminathan, Suresh Kumar Kirtane, Ameya Chen, Yibu Panyam, Jayanth Machida, Keigo |
author_sort | Chen, Chia‐Lin |
collection | PubMed |
description | A critical barrier to effective cancer therapy is the improvement of drug selectivity, toxicity, and reduced recurrence of tumors expanded from tumor‐initiating stem‐like cells (TICs). The aim is to identify circulating tumor cell (CTC)‐biomarkers and to identify an effective combination of TIC‐specific, repurposed federal drug administration (FDA)‐approved drugs. Three different types of high‐throughput screens targeting the TIC population are employed: these include a CD133 (+) cell viability screen, a NANOG expression screen, and a drug combination screen. When combined in a refined secondary screening approach that targets Nanog expression with the same FDA‐approved drug library, histone deacetylase (HDAC) inhibitor(s) combined with all‐trans retinoic acid (ATRA) demonstrate the highest efficacy for inhibition of TIC growth in vitro and in vivo. Addition of immune checkpoint inhibitor further decreases recurrence and extends PDX mouse survival. RNA‐seq analysis of TICs reveals that combined drug treatment reduces many Toll‐like receptors (TLR) and stemness genes through repression of the lncRNA MIR22HG. This downregulation induces PTEN and TET2, leading to loss of the self‐renewal property of TICs. Thus, CTC biomarker analysis would predict the prognosis and therapy response to this drug combination. In general, biomarker‐guided stratification of HCC patients and TIC‐targeted therapy should eradicate TICs to extend HCC patient survival. |
format | Online Article Text |
id | pubmed-10190641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101906412023-05-18 Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells Chen, Chia‐Lin Hernandez, Juan Carlos Uthaya Kumar, Dinesh Babu Machida, Tatsuya Tahara, Stanley M. El‐Khoueiry, Anthony Li, Meng Punj, Vasu Swaminathan, Suresh Kumar Kirtane, Ameya Chen, Yibu Panyam, Jayanth Machida, Keigo Adv Sci (Weinh) Research Articles A critical barrier to effective cancer therapy is the improvement of drug selectivity, toxicity, and reduced recurrence of tumors expanded from tumor‐initiating stem‐like cells (TICs). The aim is to identify circulating tumor cell (CTC)‐biomarkers and to identify an effective combination of TIC‐specific, repurposed federal drug administration (FDA)‐approved drugs. Three different types of high‐throughput screens targeting the TIC population are employed: these include a CD133 (+) cell viability screen, a NANOG expression screen, and a drug combination screen. When combined in a refined secondary screening approach that targets Nanog expression with the same FDA‐approved drug library, histone deacetylase (HDAC) inhibitor(s) combined with all‐trans retinoic acid (ATRA) demonstrate the highest efficacy for inhibition of TIC growth in vitro and in vivo. Addition of immune checkpoint inhibitor further decreases recurrence and extends PDX mouse survival. RNA‐seq analysis of TICs reveals that combined drug treatment reduces many Toll‐like receptors (TLR) and stemness genes through repression of the lncRNA MIR22HG. This downregulation induces PTEN and TET2, leading to loss of the self‐renewal property of TICs. Thus, CTC biomarker analysis would predict the prognosis and therapy response to this drug combination. In general, biomarker‐guided stratification of HCC patients and TIC‐targeted therapy should eradicate TICs to extend HCC patient survival. John Wiley and Sons Inc. 2023-03-22 /pmc/articles/PMC10190641/ /pubmed/36949364 http://dx.doi.org/10.1002/advs.202206812 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Chen, Chia‐Lin Hernandez, Juan Carlos Uthaya Kumar, Dinesh Babu Machida, Tatsuya Tahara, Stanley M. El‐Khoueiry, Anthony Li, Meng Punj, Vasu Swaminathan, Suresh Kumar Kirtane, Ameya Chen, Yibu Panyam, Jayanth Machida, Keigo Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title | Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title_full | Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title_fullStr | Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title_full_unstemmed | Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title_short | Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor‐Initiating Stem‐Like Cells |
title_sort | profiling of circulating tumor cells for screening of selective inhibitors of tumor‐initiating stem‐like cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10190641/ https://www.ncbi.nlm.nih.gov/pubmed/36949364 http://dx.doi.org/10.1002/advs.202206812 |
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