Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer.

Abstract:

:Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Drugs targeting the renin-angiotensin system, normally prescribed to treat hypertension, inhibit fibroblast contraction and extracellular matrix deposition, thereby reducing liver metastases stiffening and increasing the anti-angiogenic effects of bevacizumab. Patients treated with bevacizumab showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, highlighting the importance of modulating the mechanical microenvironment for therapeutic regimens.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Shen Y,Wang X,Lu J,Salfenmoser M,Wirsik NM,Schleussner N,Imle A,Freire Valls A,Radhakrishnan P,Liang J,Wang G,Muley T,Schneider M,Ruiz de Almodovar C,Diz-Muñoz A,Schmidt T

doi

10.1016/j.ccell.2020.05.005

subject

Has Abstract

pub_date

2020-06-08 00:00:00

pages

800-817.e7

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(20)30255-5

journal_volume

37

pub_type

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