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RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that primarily originate from the bile duct. Tumor heterogeneity is a prime characteristic of CCA and considering the scarcity of approved targeted therapy drugs, this makes precision oncology impractical in CCA. Stratifying patients...

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Autores principales: Balasubramanian, Brinda, Venkatraman, Simran, Janvilisri, Tavan, Suthiphongchai, Tuangporn, Jitkaew, Siriporn, Sripa, Jittiyawadee, Tohtong, Rutaiwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469883/
https://www.ncbi.nlm.nih.gov/pubmed/34577598
http://dx.doi.org/10.3390/ph14090898
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author Balasubramanian, Brinda
Venkatraman, Simran
Janvilisri, Tavan
Suthiphongchai, Tuangporn
Jitkaew, Siriporn
Sripa, Jittiyawadee
Tohtong, Rutaiwan
author_facet Balasubramanian, Brinda
Venkatraman, Simran
Janvilisri, Tavan
Suthiphongchai, Tuangporn
Jitkaew, Siriporn
Sripa, Jittiyawadee
Tohtong, Rutaiwan
author_sort Balasubramanian, Brinda
collection PubMed
description Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that primarily originate from the bile duct. Tumor heterogeneity is a prime characteristic of CCA and considering the scarcity of approved targeted therapy drugs, this makes precision oncology impractical in CCA. Stratifying patients based on their molecular signature and biomarker-guided therapy may offer a conducive solution. Receptors tyrosine kinases (RTK) are potential targets for novel therapeutic strategies in CCA as RTK signaling is dysregulated in CCA. This study aims to identify targetable RTK profile in CCA using a bioinformatic approach. We discovered that CCA samples could be grouped into molecular subtypes based on the gene expression profile of selected RTKs (RTK25). Using the RTK25 gene list, we discovered five distinct molecular subtypes of CCA in this cohort. Tyrosine kinase inhibitors that target each RTK profile and their subsequent molecular signatures were also discovered. These results suggest that certain RTKs correlate with each other, indicating that tailored dual inhibition of RTKs may be more favorable than monotherapy. The results from this study can direct future investigative attention towards validating this concept in in vivo and in vitro systems. Ultimately, this will facilitate biomarker-guided clinical trials for the successful approval of novel therapeutic options in CCA.
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spelling pubmed-84698832021-09-27 RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach Balasubramanian, Brinda Venkatraman, Simran Janvilisri, Tavan Suthiphongchai, Tuangporn Jitkaew, Siriporn Sripa, Jittiyawadee Tohtong, Rutaiwan Pharmaceuticals (Basel) Article Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that primarily originate from the bile duct. Tumor heterogeneity is a prime characteristic of CCA and considering the scarcity of approved targeted therapy drugs, this makes precision oncology impractical in CCA. Stratifying patients based on their molecular signature and biomarker-guided therapy may offer a conducive solution. Receptors tyrosine kinases (RTK) are potential targets for novel therapeutic strategies in CCA as RTK signaling is dysregulated in CCA. This study aims to identify targetable RTK profile in CCA using a bioinformatic approach. We discovered that CCA samples could be grouped into molecular subtypes based on the gene expression profile of selected RTKs (RTK25). Using the RTK25 gene list, we discovered five distinct molecular subtypes of CCA in this cohort. Tyrosine kinase inhibitors that target each RTK profile and their subsequent molecular signatures were also discovered. These results suggest that certain RTKs correlate with each other, indicating that tailored dual inhibition of RTKs may be more favorable than monotherapy. The results from this study can direct future investigative attention towards validating this concept in in vivo and in vitro systems. Ultimately, this will facilitate biomarker-guided clinical trials for the successful approval of novel therapeutic options in CCA. MDPI 2021-09-03 /pmc/articles/PMC8469883/ /pubmed/34577598 http://dx.doi.org/10.3390/ph14090898 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Balasubramanian, Brinda
Venkatraman, Simran
Janvilisri, Tavan
Suthiphongchai, Tuangporn
Jitkaew, Siriporn
Sripa, Jittiyawadee
Tohtong, Rutaiwan
RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title_full RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title_fullStr RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title_full_unstemmed RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title_short RTK25: A Comprehensive Molecular Profiling Strategy in Cholangiocarcinoma Using an Integrated Bioinformatics Approach
title_sort rtk25: a comprehensive molecular profiling strategy in cholangiocarcinoma using an integrated bioinformatics approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469883/
https://www.ncbi.nlm.nih.gov/pubmed/34577598
http://dx.doi.org/10.3390/ph14090898
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