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Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact

SIMPLE SUMMARY: Although much progress has been made in recent years in the clinical management of solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with limited therapeutical options. Indeed, responses to standard chemotherapy and targeted therapies vary widely when adminis...

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Autores principales: Gutiérrez, María Laura, Muñoz-Bellvís, Luis, Orfao, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430663/
https://www.ncbi.nlm.nih.gov/pubmed/34503261
http://dx.doi.org/10.3390/cancers13174451
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author Gutiérrez, María Laura
Muñoz-Bellvís, Luis
Orfao, Alberto
author_facet Gutiérrez, María Laura
Muñoz-Bellvís, Luis
Orfao, Alberto
author_sort Gutiérrez, María Laura
collection PubMed
description SIMPLE SUMMARY: Although much progress has been made in recent years in the clinical management of solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with limited therapeutical options. Indeed, responses to standard chemotherapy and targeted therapies vary widely when administered to unselected patient populations. This is in part due to the heterogeneous and variable molecular profile of PDAC. Here, we review current knowledge about the genomic heterogeneity of PDAC and its impact on disease behavior, and treatment including the molecular mechanisms of chemoresistance. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death due to limited advances in recent years in early diagnosis and personalized therapy capable of overcoming tumor resistance to chemotherapy. In the last decades, significant advances have been achieved in the identification of recurrent genetic and molecular alterations of PDAC including those involving the KRAS, CDKN2A, SMAD4, and TP53 driver genes. Despite these common genetic traits, PDAC are highly heterogeneous tumors at both the inter- and intra-tumoral genomic level, which might contribute to distinct tumor behavior and response to therapy, with variable patient outcomes. Despite this, genetic and genomic data on PDAC has had a limited impact on the clinical management of patients. Integration of genomic data for classification of PDAC into clinically defined entities—i.e., classical vs. squamous subtypes of PDAC—leading to different treatment approaches has the potential for significantly improving patient outcomes. In this review, we summarize current knowledge about the most relevant genomic subtypes of PDAC including the impact of distinct patterns of intra-tumoral genomic heterogeneity on the classification and clinical and therapeutic management of PDAC.
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spelling pubmed-84306632021-09-11 Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact Gutiérrez, María Laura Muñoz-Bellvís, Luis Orfao, Alberto Cancers (Basel) Review SIMPLE SUMMARY: Although much progress has been made in recent years in the clinical management of solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with limited therapeutical options. Indeed, responses to standard chemotherapy and targeted therapies vary widely when administered to unselected patient populations. This is in part due to the heterogeneous and variable molecular profile of PDAC. Here, we review current knowledge about the genomic heterogeneity of PDAC and its impact on disease behavior, and treatment including the molecular mechanisms of chemoresistance. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death due to limited advances in recent years in early diagnosis and personalized therapy capable of overcoming tumor resistance to chemotherapy. In the last decades, significant advances have been achieved in the identification of recurrent genetic and molecular alterations of PDAC including those involving the KRAS, CDKN2A, SMAD4, and TP53 driver genes. Despite these common genetic traits, PDAC are highly heterogeneous tumors at both the inter- and intra-tumoral genomic level, which might contribute to distinct tumor behavior and response to therapy, with variable patient outcomes. Despite this, genetic and genomic data on PDAC has had a limited impact on the clinical management of patients. Integration of genomic data for classification of PDAC into clinically defined entities—i.e., classical vs. squamous subtypes of PDAC—leading to different treatment approaches has the potential for significantly improving patient outcomes. In this review, we summarize current knowledge about the most relevant genomic subtypes of PDAC including the impact of distinct patterns of intra-tumoral genomic heterogeneity on the classification and clinical and therapeutic management of PDAC. MDPI 2021-09-03 /pmc/articles/PMC8430663/ /pubmed/34503261 http://dx.doi.org/10.3390/cancers13174451 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 Review
Gutiérrez, María Laura
Muñoz-Bellvís, Luis
Orfao, Alberto
Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title_full Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title_fullStr Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title_full_unstemmed Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title_short Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact
title_sort genomic heterogeneity of pancreatic ductal adenocarcinoma and its clinical impact
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430663/
https://www.ncbi.nlm.nih.gov/pubmed/34503261
http://dx.doi.org/10.3390/cancers13174451
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