A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer

Stefano Coppola, Ilaria Carnevale, Erik H.J. Danen, Godefridus J. Peters, Thomas Schmidt, Yehuda G. Assaraf, Elisa Giovannetti

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy. This chemoresistant phenotype has been historically associated with genetic factors. Major biomedical research efforts were concentrated that resulted in the identification of subtypes characterized by specific genetic lesions and gene expression signatures that suggest important biological differences. However, to date, these distinct differences could not be exploited for therapeutic interventions. Apart from these genetic factors, desmoplasia and tumor microenvironment have been recognized as key contributors to PDAC chemoresistance. However, while several strategies targeting tumor-stroma have been explored including drugs against members of the Hedgehog family, they failed to meet the expectations in the clinical setting. These unsatisfactory clinical results suggest that, an important link between genetics and the influence of tumor microenvironment on PDAC chemoresistance remains to be elucidated. In this respect, mechanobiology is an emerging multidisciplinary field that encompasses cell and developmental biology as well as biophysics and bioengineering. Herein we provide a comprehensive overview of the key players in pancreatic cancer chemoresistance from the perspective of mechanobiology, and discuss novel experimental avenues such as elastic micropillar arrays that could provide fresh insights for the development of mechanobiology-targeted therapeutic approaches (know as mechanobology) to overcome anticancer drug resistance in pancreatic cancer.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalDrug Resistance Updates
Volume31
DOIs
Publication statusPublished - 1 Mar 2017

Cite this

Coppola, Stefano ; Carnevale, Ilaria ; Danen, Erik H.J. ; Peters, Godefridus J. ; Schmidt, Thomas ; Assaraf, Yehuda G. ; Giovannetti, Elisa. / A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer. In: Drug Resistance Updates. 2017 ; Vol. 31. pp. 43-51.
@article{c11f01ecf3aa48068ff00651815454a3,
title = "A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy. This chemoresistant phenotype has been historically associated with genetic factors. Major biomedical research efforts were concentrated that resulted in the identification of subtypes characterized by specific genetic lesions and gene expression signatures that suggest important biological differences. However, to date, these distinct differences could not be exploited for therapeutic interventions. Apart from these genetic factors, desmoplasia and tumor microenvironment have been recognized as key contributors to PDAC chemoresistance. However, while several strategies targeting tumor-stroma have been explored including drugs against members of the Hedgehog family, they failed to meet the expectations in the clinical setting. These unsatisfactory clinical results suggest that, an important link between genetics and the influence of tumor microenvironment on PDAC chemoresistance remains to be elucidated. In this respect, mechanobiology is an emerging multidisciplinary field that encompasses cell and developmental biology as well as biophysics and bioengineering. Herein we provide a comprehensive overview of the key players in pancreatic cancer chemoresistance from the perspective of mechanobiology, and discuss novel experimental avenues such as elastic micropillar arrays that could provide fresh insights for the development of mechanobiology-targeted therapeutic approaches (know as mechanobology) to overcome anticancer drug resistance in pancreatic cancer.",
keywords = "Chemoresistance, Elastic microvillar arrays, Integrins, Mechanobiology, Mechanopharmacology, Mechanosensing/mechanotransduction, Multi-cellular 3D systems, Pancreatic cancer, Prognostic/predictive markers, Rheometry, Support-based cell stretcher, Traction force microscopy, Tumor microenvironment",
author = "Stefano Coppola and Ilaria Carnevale and Danen, {Erik H.J.} and Peters, {Godefridus J.} and Thomas Schmidt and Assaraf, {Yehuda G.} and Elisa Giovannetti",
year = "2017",
month = "3",
day = "1",
doi = "10.1016/j.drup.2017.07.001",
language = "English",
volume = "31",
pages = "43--51",
journal = "Drug Resistance Updates",
issn = "1368-7646",
publisher = "Churchill Livingstone",

}

A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer. / Coppola, Stefano; Carnevale, Ilaria; Danen, Erik H.J.; Peters, Godefridus J.; Schmidt, Thomas; Assaraf, Yehuda G.; Giovannetti, Elisa.

In: Drug Resistance Updates, Vol. 31, 01.03.2017, p. 43-51.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer

AU - Coppola, Stefano

AU - Carnevale, Ilaria

AU - Danen, Erik H.J.

AU - Peters, Godefridus J.

AU - Schmidt, Thomas

AU - Assaraf, Yehuda G.

AU - Giovannetti, Elisa

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy. This chemoresistant phenotype has been historically associated with genetic factors. Major biomedical research efforts were concentrated that resulted in the identification of subtypes characterized by specific genetic lesions and gene expression signatures that suggest important biological differences. However, to date, these distinct differences could not be exploited for therapeutic interventions. Apart from these genetic factors, desmoplasia and tumor microenvironment have been recognized as key contributors to PDAC chemoresistance. However, while several strategies targeting tumor-stroma have been explored including drugs against members of the Hedgehog family, they failed to meet the expectations in the clinical setting. These unsatisfactory clinical results suggest that, an important link between genetics and the influence of tumor microenvironment on PDAC chemoresistance remains to be elucidated. In this respect, mechanobiology is an emerging multidisciplinary field that encompasses cell and developmental biology as well as biophysics and bioengineering. Herein we provide a comprehensive overview of the key players in pancreatic cancer chemoresistance from the perspective of mechanobiology, and discuss novel experimental avenues such as elastic micropillar arrays that could provide fresh insights for the development of mechanobiology-targeted therapeutic approaches (know as mechanobology) to overcome anticancer drug resistance in pancreatic cancer.

AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy. This chemoresistant phenotype has been historically associated with genetic factors. Major biomedical research efforts were concentrated that resulted in the identification of subtypes characterized by specific genetic lesions and gene expression signatures that suggest important biological differences. However, to date, these distinct differences could not be exploited for therapeutic interventions. Apart from these genetic factors, desmoplasia and tumor microenvironment have been recognized as key contributors to PDAC chemoresistance. However, while several strategies targeting tumor-stroma have been explored including drugs against members of the Hedgehog family, they failed to meet the expectations in the clinical setting. These unsatisfactory clinical results suggest that, an important link between genetics and the influence of tumor microenvironment on PDAC chemoresistance remains to be elucidated. In this respect, mechanobiology is an emerging multidisciplinary field that encompasses cell and developmental biology as well as biophysics and bioengineering. Herein we provide a comprehensive overview of the key players in pancreatic cancer chemoresistance from the perspective of mechanobiology, and discuss novel experimental avenues such as elastic micropillar arrays that could provide fresh insights for the development of mechanobiology-targeted therapeutic approaches (know as mechanobology) to overcome anticancer drug resistance in pancreatic cancer.

KW - Chemoresistance

KW - Elastic microvillar arrays

KW - Integrins

KW - Mechanobiology

KW - Mechanopharmacology

KW - Mechanosensing/mechanotransduction

KW - Multi-cellular 3D systems

KW - Pancreatic cancer

KW - Prognostic/predictive markers

KW - Rheometry

KW - Support-based cell stretcher

KW - Traction force microscopy

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85026757333&partnerID=8YFLogxK

U2 - 10.1016/j.drup.2017.07.001

DO - 10.1016/j.drup.2017.07.001

M3 - Article

VL - 31

SP - 43

EP - 51

JO - Drug Resistance Updates

JF - Drug Resistance Updates

SN - 1368-7646

ER -