Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer

Pancreatic cancer is one of the deadliest cancers and remains a major unsolved health problem. While pancreatic ductal adenocarcinoma (PDAC) is associated with driver mutations in only four major genes (KRAS, TP53, SMAD4, and CDKN2A), every tumor differs in its molecular landscape, histology, and pr...

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Autores principales:	Sushmitha Sankarasubramanian, Ulrike Pfohl, Christian R. A. Regenbrecht, Christoph Reinhard, Lena Wedeken
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity KRAS 3D cell culture models personalized medicine patient-derived tumor organoids Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/16fe49992be043d99450bb2184646f46
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spelling	oai:doaj.org-article:16fe49992be043d99450bb2184646f462021-11-04T06:28:35ZContext Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer2296-634X10.3389/fcell.2021.760705https://doaj.org/article/16fe49992be043d99450bb2184646f462021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.760705/fullhttps://doaj.org/toc/2296-634XPancreatic cancer is one of the deadliest cancers and remains a major unsolved health problem. While pancreatic ductal adenocarcinoma (PDAC) is associated with driver mutations in only four major genes (KRAS, TP53, SMAD4, and CDKN2A), every tumor differs in its molecular landscape, histology, and prognosis. It is crucial to understand and consider these differences to be able to tailor treatment regimens specific to the vulnerabilities of the individual tumor to enhance patient outcome. This review focuses on the heterogeneity of pancreatic tumor cells and how in addition to genetic alterations, the subsequent dysregulation of multiple signaling cascades at various levels, epigenetic and metabolic factors contribute to the oncogenesis of PDAC and compensate for each other in driving cancer progression if one is tackled by a therapeutic approach. This implicates that besides the need for new combinatorial therapies for PDAC, a personalized approach for treating this highly complex cancer is required. A strategy that combines both a target-based and phenotypic approach to identify an effective treatment, like Reverse Clinical Engineering® using patient-derived organoids, is discussed as a promising way forward in the field of personalized medicine to tackle this deadly disease.Sushmitha SankarasubramanianSushmitha SankarasubramanianUlrike PfohlUlrike PfohlUlrike PfohlChristian R. A. RegenbrechtChristian R. A. RegenbrechtChristian R. A. RegenbrechtChristoph ReinhardChristoph ReinhardLena WedekenLena WedekenFrontiers Media S.A.articlepancreatic ductal adenocarcinoma (PDAC)tumor heterogeneityKRAS3D cell culture modelspersonalized medicinepatient-derived tumor organoidsBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity KRAS 3D cell culture models personalized medicine patient-derived tumor organoids Biology (General) QH301-705.5
spellingShingle	pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity KRAS 3D cell culture models personalized medicine patient-derived tumor organoids Biology (General) QH301-705.5 Sushmitha Sankarasubramanian Sushmitha Sankarasubramanian Ulrike Pfohl Ulrike Pfohl Ulrike Pfohl Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christoph Reinhard Christoph Reinhard Lena Wedeken Lena Wedeken Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
description	Pancreatic cancer is one of the deadliest cancers and remains a major unsolved health problem. While pancreatic ductal adenocarcinoma (PDAC) is associated with driver mutations in only four major genes (KRAS, TP53, SMAD4, and CDKN2A), every tumor differs in its molecular landscape, histology, and prognosis. It is crucial to understand and consider these differences to be able to tailor treatment regimens specific to the vulnerabilities of the individual tumor to enhance patient outcome. This review focuses on the heterogeneity of pancreatic tumor cells and how in addition to genetic alterations, the subsequent dysregulation of multiple signaling cascades at various levels, epigenetic and metabolic factors contribute to the oncogenesis of PDAC and compensate for each other in driving cancer progression if one is tackled by a therapeutic approach. This implicates that besides the need for new combinatorial therapies for PDAC, a personalized approach for treating this highly complex cancer is required. A strategy that combines both a target-based and phenotypic approach to identify an effective treatment, like Reverse Clinical Engineering® using patient-derived organoids, is discussed as a promising way forward in the field of personalized medicine to tackle this deadly disease.
format	article
author	Sushmitha Sankarasubramanian Sushmitha Sankarasubramanian Ulrike Pfohl Ulrike Pfohl Ulrike Pfohl Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christoph Reinhard Christoph Reinhard Lena Wedeken Lena Wedeken
author_facet	Sushmitha Sankarasubramanian Sushmitha Sankarasubramanian Ulrike Pfohl Ulrike Pfohl Ulrike Pfohl Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christian R. A. Regenbrecht Christoph Reinhard Christoph Reinhard Lena Wedeken Lena Wedeken
author_sort	Sushmitha Sankarasubramanian
title	Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
title_short	Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
title_full	Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
title_fullStr	Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
title_full_unstemmed	Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
title_sort	context matters—why we need to change from a one size fits all approach to made-to-measure therapies for individual patients with pancreatic cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/16fe49992be043d99450bb2184646f46
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Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer

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