Nuclear Export Inhibition for Pancreatic Cancer Therapy
Pancreatic cancer is a deadly disease that is resistant to most available therapeutics. Pancreatic cancer to date has no effective drugs that could enhance the survival of patients once their disease has metastasized. There is a need for the identification of novel actionable drug targets in this un...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-05-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/10/5/138 |
| _version_ | 1797707820780486656 |
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| author | Irfana Muqbil Asfar S. Azmi Ramzi M. Mohammad |
| author_facet | Irfana Muqbil Asfar S. Azmi Ramzi M. Mohammad |
| author_sort | Irfana Muqbil |
| collection | DOAJ |
| description | Pancreatic cancer is a deadly disease that is resistant to most available therapeutics. Pancreatic cancer to date has no effective drugs that could enhance the survival of patients once their disease has metastasized. There is a need for the identification of novel actionable drug targets in this unusually recalcitrant cancer. Nuclear protein transport is an important mechanism that regulates the function of several tumor suppressor proteins (TSPs) in a compartmentalization-dependent manner. High expression of the nuclear exporter chromosome maintenance region 1 (CRM1) or exportin 1 (XPO1), a common feature of several cancers including pancreatic cancer, results in excessive export of critical TSPs to the incorrect cellular compartment, leading to their functional inactivation. Small molecule inhibitors of XPO1 can block this export, retaining very important and functional TSPs in the nucleus and leading to the effective killing of the cancer cells. This review highlights the current knowledge on the role of XPO1 in pancreatic cancer and how this serves as a unique and clinically viable target in this devastating and by far incurable cancer. |
| first_indexed | 2024-03-12T06:12:12Z |
| format | Article |
| id | doaj.art-d9b481dd91c04c2089363e6f2c0ef9d3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:12:12Z |
| publishDate | 2018-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d9b481dd91c04c2089363e6f2c0ef9d32023-09-03T02:56:36ZengMDPI AGCancers2072-66942018-05-0110513810.3390/cancers10050138cancers10050138Nuclear Export Inhibition for Pancreatic Cancer TherapyIrfana Muqbil0Asfar S. Azmi1Ramzi M. Mohammad2Department of Chemistry, University of Detroit Mercy, Detroit, MI 48221, USADepartment of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USAPancreatic cancer is a deadly disease that is resistant to most available therapeutics. Pancreatic cancer to date has no effective drugs that could enhance the survival of patients once their disease has metastasized. There is a need for the identification of novel actionable drug targets in this unusually recalcitrant cancer. Nuclear protein transport is an important mechanism that regulates the function of several tumor suppressor proteins (TSPs) in a compartmentalization-dependent manner. High expression of the nuclear exporter chromosome maintenance region 1 (CRM1) or exportin 1 (XPO1), a common feature of several cancers including pancreatic cancer, results in excessive export of critical TSPs to the incorrect cellular compartment, leading to their functional inactivation. Small molecule inhibitors of XPO1 can block this export, retaining very important and functional TSPs in the nucleus and leading to the effective killing of the cancer cells. This review highlights the current knowledge on the role of XPO1 in pancreatic cancer and how this serves as a unique and clinically viable target in this devastating and by far incurable cancer.http://www.mdpi.com/2072-6694/10/5/138Pancreatic CancerPancreatic Ductal Adenocarcinomanuclear protein exportExportin-1CRM1Specific Inhibitors of Nuclear ExportSINEPhase I |
| spellingShingle | Irfana Muqbil Asfar S. Azmi Ramzi M. Mohammad Nuclear Export Inhibition for Pancreatic Cancer Therapy Cancers Pancreatic Cancer Pancreatic Ductal Adenocarcinoma nuclear protein export Exportin-1 CRM1 Specific Inhibitors of Nuclear Export SINE Phase I |
| title | Nuclear Export Inhibition for Pancreatic Cancer Therapy |
| title_full | Nuclear Export Inhibition for Pancreatic Cancer Therapy |
| title_fullStr | Nuclear Export Inhibition for Pancreatic Cancer Therapy |
| title_full_unstemmed | Nuclear Export Inhibition for Pancreatic Cancer Therapy |
| title_short | Nuclear Export Inhibition for Pancreatic Cancer Therapy |
| title_sort | nuclear export inhibition for pancreatic cancer therapy |
| topic | Pancreatic Cancer Pancreatic Ductal Adenocarcinoma nuclear protein export Exportin-1 CRM1 Specific Inhibitors of Nuclear Export SINE Phase I |
| url | http://www.mdpi.com/2072-6694/10/5/138 |
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