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Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to low therapeutic response rates and poor prognoses. Majority of patients present with symptoms post metastatic spread, which contributes to its overall lethality as the 4th leading cause of cancer-related deaths. Ther...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843014/ https://www.ncbi.nlm.nih.gov/pubmed/35174086 http://dx.doi.org/10.3389/fonc.2022.809179 |
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author | Angstadt, Shantel Zhu, Qingfeng Jaffee, Elizabeth M. Robinson, Douglas N. Anders, Robert A. |
author_facet | Angstadt, Shantel Zhu, Qingfeng Jaffee, Elizabeth M. Robinson, Douglas N. Anders, Robert A. |
author_sort | Angstadt, Shantel |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to low therapeutic response rates and poor prognoses. Majority of patients present with symptoms post metastatic spread, which contributes to its overall lethality as the 4th leading cause of cancer-related deaths. Therapeutic approaches thus far target only one or two of the cancer specific hallmarks, such as high proliferation rate, apoptotic evasion, or immune evasion. Recent genomic discoveries reveal that genetic heterogeneity, early micrometastases, and an immunosuppressive tumor microenvironment contribute to the inefficacy of current standard treatments and specific molecular-targeted therapies. To effectively combat cancers like PDAC, we need an innovative approach that can simultaneously impact the multiple hallmarks driving cancer progression. Here, we present the mechanical properties generated by the cell’s cortical cytoskeleton, with a spotlight on PDAC, as an ideal therapeutic target that can concurrently attack multiple systems driving cancer. We start with an introduction to cancer cell mechanics and PDAC followed by a compilation of studies connecting the cortical cytoskeleton and mechanical properties to proliferation, metastasis, immune cell interactions, cancer cell stemness, and/or metabolism. We further elaborate on the implications of these findings in disease progression, therapeutic resistance, and clinical relapse. Manipulation of the cancer cell’s mechanical system has already been shown to prevent metastasis in preclinical models, but it has greater potential for target exploration since it is a foundational property of the cell that regulates various oncogenic behaviors. |
format | Online Article Text |
id | pubmed-8843014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88430142022-02-15 Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications Angstadt, Shantel Zhu, Qingfeng Jaffee, Elizabeth M. Robinson, Douglas N. Anders, Robert A. Front Oncol Oncology Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to low therapeutic response rates and poor prognoses. Majority of patients present with symptoms post metastatic spread, which contributes to its overall lethality as the 4th leading cause of cancer-related deaths. Therapeutic approaches thus far target only one or two of the cancer specific hallmarks, such as high proliferation rate, apoptotic evasion, or immune evasion. Recent genomic discoveries reveal that genetic heterogeneity, early micrometastases, and an immunosuppressive tumor microenvironment contribute to the inefficacy of current standard treatments and specific molecular-targeted therapies. To effectively combat cancers like PDAC, we need an innovative approach that can simultaneously impact the multiple hallmarks driving cancer progression. Here, we present the mechanical properties generated by the cell’s cortical cytoskeleton, with a spotlight on PDAC, as an ideal therapeutic target that can concurrently attack multiple systems driving cancer. We start with an introduction to cancer cell mechanics and PDAC followed by a compilation of studies connecting the cortical cytoskeleton and mechanical properties to proliferation, metastasis, immune cell interactions, cancer cell stemness, and/or metabolism. We further elaborate on the implications of these findings in disease progression, therapeutic resistance, and clinical relapse. Manipulation of the cancer cell’s mechanical system has already been shown to prevent metastasis in preclinical models, but it has greater potential for target exploration since it is a foundational property of the cell that regulates various oncogenic behaviors. Frontiers Media S.A. 2022-01-31 /pmc/articles/PMC8843014/ /pubmed/35174086 http://dx.doi.org/10.3389/fonc.2022.809179 Text en Copyright © 2022 Angstadt, Zhu, Jaffee, Robinson and Anders 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 | Oncology Angstadt, Shantel Zhu, Qingfeng Jaffee, Elizabeth M. Robinson, Douglas N. Anders, Robert A. Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title | Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title_full | Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title_fullStr | Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title_full_unstemmed | Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title_short | Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications |
title_sort | pancreatic ductal adenocarcinoma cortical mechanics and clinical implications |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843014/ https://www.ncbi.nlm.nih.gov/pubmed/35174086 http://dx.doi.org/10.3389/fonc.2022.809179 |
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