Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems

Katja Peschke; Hannah Jakubowsky; Arlett Schäfer; Carlo Maurer; Sebastian Lange; Felix Orben; Raquel Bernad; Felix N. Harder; Matthias Eiber; Rupert Öllinger; Katja Steiger; Melissa Schlitter; Wilko Weichert; Ulrich Mayr; Veit Phillip; Christoph Schlag; Roland M. Schmid; Rickmer F. Braren; Bo Kong; Ihsan Ekin Demir; Helmut Friess; Roland Rad; Dieter Saur; Günter Schneider; Maximilian Reichert

doi:10.15252/emmm.202114876

Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems

Katja Peschke, Hannah Jakubowsky, Arlett Schäfer, Carlo Maurer, Sebastian Lange, Felix Orben, Raquel Bernad, Felix N. Harder, Matthias Eiber, Rupert Öllinger, Katja Steiger, Melissa Schlitter, Wilko Weichert, Ulrich Mayr, Veit Phillip, Christoph Schlag, Roland M. Schmid, Rickmer F. Braren, Bo Kong, Ihsan Ekin DemirHelmut Friess, Roland Rad, Dieter Saur, Günter Schneider, Maximilian Reichert

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.

Original language	English
Article number	e14876
Journal	EMBO Molecular Medicine
Volume	14
Issue number	4
DOIs	https://doi.org/10.15252/emmm.202114876
State	Published - 7 Apr 2022

Keywords

functional screening
pancreatic cancer
precision oncology
therapy-induced vulnerabilities
tumor cell plasticity

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10.15252/emmm.202114876

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Peschke, K., Jakubowsky, H., Schäfer, A., Maurer, C., Lange, S., Orben, F., Bernad, R., Harder, F. N., Eiber, M., Öllinger, R., Steiger, K., Schlitter, M., Weichert, W., Mayr, U., Phillip, V., Schlag, C., Schmid, R. M., Braren, R. F., Kong, B., ... Reichert, M. (2022). Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems. EMBO Molecular Medicine, 14(4), Article e14876. https://doi.org/10.15252/emmm.202114876

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title = "Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems",

abstract = "Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.",

keywords = "functional screening, pancreatic cancer, precision oncology, therapy-induced vulnerabilities, tumor cell plasticity",

author = "Katja Peschke and Hannah Jakubowsky and Arlett Sch{\"a}fer and Carlo Maurer and Sebastian Lange and Felix Orben and Raquel Bernad and Harder, {Felix N.} and Matthias Eiber and Rupert {\"O}llinger and Katja Steiger and Melissa Schlitter and Wilko Weichert and Ulrich Mayr and Veit Phillip and Christoph Schlag and Schmid, {Roland M.} and Braren, {Rickmer F.} and Bo Kong and Demir, {Ihsan Ekin} and Helmut Friess and Roland Rad and Dieter Saur and G{\"u}nter Schneider and Maximilian Reichert",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY 4.0 license.",

year = "2022",

month = apr,

day = "7",

doi = "10.15252/emmm.202114876",

language = "English",

volume = "14",

journal = "EMBO Molecular Medicine",

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Peschke, K, Jakubowsky, H, Schäfer, A, Maurer, C, Lange, S, Orben, F, Bernad, R, Harder, FN, Eiber, M, Öllinger, R, Steiger, K, Schlitter, M, Weichert, W, Mayr, U, Phillip, V, Schlag, C, Schmid, RM, Braren, RF, Kong, B, Demir, IE , Friess, H , Rad, R , Saur, D, Schneider, G & Reichert, M 2022, 'Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems', EMBO Molecular Medicine, vol. 14, no. 4, e14876. https://doi.org/10.15252/emmm.202114876

TY - JOUR

T1 - Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems

AU - Peschke, Katja

AU - Jakubowsky, Hannah

AU - Schäfer, Arlett

AU - Maurer, Carlo

AU - Lange, Sebastian

AU - Orben, Felix

AU - Bernad, Raquel

AU - Harder, Felix N.

AU - Eiber, Matthias

AU - Öllinger, Rupert

AU - Steiger, Katja

AU - Schlitter, Melissa

AU - Weichert, Wilko

AU - Mayr, Ulrich

AU - Phillip, Veit

AU - Schlag, Christoph

AU - Schmid, Roland M.

AU - Braren, Rickmer F.

AU - Kong, Bo

AU - Demir, Ihsan Ekin

AU - Friess, Helmut

AU - Rad, Roland

AU - Saur, Dieter

AU - Schneider, Günter

AU - Reichert, Maximilian

PY - 2022/4/7

Y1 - 2022/4/7

N2 - Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.

AB - Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.

KW - functional screening

KW - pancreatic cancer

KW - precision oncology

KW - therapy-induced vulnerabilities

KW - tumor cell plasticity

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DO - 10.15252/emmm.202114876

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AN - SCOPUS:85124394032

SN - 1757-4676

VL - 14

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 4

M1 - e14876

ER -

Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems

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