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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.809179/full |
| _version_ | 1818715933246488576 |
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| author | Shantel Angstadt Shantel Angstadt Shantel Angstadt Qingfeng Zhu Elizabeth M. Jaffee Douglas N. Robinson Douglas N. Robinson Robert A. Anders |
| author_facet | Shantel Angstadt Shantel Angstadt Shantel Angstadt Qingfeng Zhu Elizabeth M. Jaffee Douglas N. Robinson Douglas N. Robinson Robert A. Anders |
| author_sort | Shantel Angstadt |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T19:11:14Z |
| format | Article |
| id | doaj.art-8fbdea4367b240f496e4f6ddb4f33b2a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T19:11:14Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8fbdea4367b240f496e4f6ddb4f33b2a2022-12-21T21:35:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011210.3389/fonc.2022.809179809179Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical ImplicationsShantel Angstadt0Shantel Angstadt1Shantel Angstadt2Qingfeng Zhu3Elizabeth M. Jaffee4Douglas N. Robinson5Douglas N. Robinson6Robert A. Anders7Department of Pathology Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Pathology Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Pathology Johns Hopkins University School of Medicine, Baltimore, MD, United StatesPancreatic 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.809179/fullPDACcytoskeletoncortical mechanicscell shapeclinical implications |
| spellingShingle | Shantel Angstadt Shantel Angstadt Shantel Angstadt Qingfeng Zhu Elizabeth M. Jaffee Douglas N. Robinson Douglas N. Robinson Robert A. Anders Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications Frontiers in Oncology PDAC cytoskeleton cortical mechanics cell shape 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 | PDAC cytoskeleton cortical mechanics cell shape clinical implications |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.809179/full |
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