Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel

Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metast...

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Autores principales:	Michael Pigula, Zhiming Mai, Sriram Anbil, Myung-Gyu Choi, Kenneth Wang, Edward Maytin, Brian Pogue, Tayyaba Hasan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	photodynamic therapy pancreatic cancer metastatic disease abscopal effect Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/612ea5ff60c2440cbadd19e1c37a4e89
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spelling	oai:doaj.org-article:612ea5ff60c2440cbadd19e1c37a4e892021-11-25T17:03:55ZDramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel10.3390/cancers132257812072-6694https://doaj.org/article/612ea5ff60c2440cbadd19e1c37a4e892021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5781https://doaj.org/toc/2072-6694Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates.Michael PigulaZhiming MaiSriram AnbilMyung-Gyu ChoiKenneth WangEdward MaytinBrian PogueTayyaba HasanMDPI AGarticlephotodynamic therapypancreatic cancermetastatic diseaseabscopal effectNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5781, p 5781 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	photodynamic therapy pancreatic cancer metastatic disease abscopal effect Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	photodynamic therapy pancreatic cancer metastatic disease abscopal effect Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Michael Pigula Zhiming Mai Sriram Anbil Myung-Gyu Choi Kenneth Wang Edward Maytin Brian Pogue Tayyaba Hasan Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
description	Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates.
format	article
author	Michael Pigula Zhiming Mai Sriram Anbil Myung-Gyu Choi Kenneth Wang Edward Maytin Brian Pogue Tayyaba Hasan
author_facet	Michael Pigula Zhiming Mai Sriram Anbil Myung-Gyu Choi Kenneth Wang Edward Maytin Brian Pogue Tayyaba Hasan
author_sort	Michael Pigula
title	Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
title_short	Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
title_full	Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
title_fullStr	Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
title_full_unstemmed	Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
title_sort	dramatic reduction of distant pancreatic metastases using local light activation of verteporfin with nab-paclitaxel
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/612ea5ff60c2440cbadd19e1c37a4e89
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Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel

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