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Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies
Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improvin...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500614/ https://www.ncbi.nlm.nih.gov/pubmed/26185420 http://dx.doi.org/10.2147/DDDT.S60328 |
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author | Chiorean, Elena Gabriela Coveler, Andrew L |
author_facet | Chiorean, Elena Gabriela Coveler, Andrew L |
author_sort | Chiorean, Elena Gabriela |
collection | PubMed |
description | Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%–90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease. |
format | Online Article Text |
id | pubmed-4500614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45006142015-07-16 Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies Chiorean, Elena Gabriela Coveler, Andrew L Drug Des Devel Ther Review Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%–90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease. Dove Medical Press 2015-07-07 /pmc/articles/PMC4500614/ /pubmed/26185420 http://dx.doi.org/10.2147/DDDT.S60328 Text en © 2015 Chiorean and Coveler. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Review Chiorean, Elena Gabriela Coveler, Andrew L Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title | Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title_full | Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title_fullStr | Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title_full_unstemmed | Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title_short | Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
title_sort | pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500614/ https://www.ncbi.nlm.nih.gov/pubmed/26185420 http://dx.doi.org/10.2147/DDDT.S60328 |
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