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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...

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Autores principales: Angstadt, Shantel, Zhu, Qingfeng, Jaffee, Elizabeth M., Robinson, Douglas N., Anders, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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