2020
DOI: 10.1172/jci136760
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Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix

Abstract: Conflict of interest: KM is an employee of Foundation Medicine. MJP serves as a consultant for Perthera and holds stock in the company. EB is an employee of Perthera. BL is an employee of Bristol-Myers Squibb. ML is an employee and shareholder of Bristol-Myers Squibb. ZJW serves as a consultant for GE Healthcare. EC has Research Funding from Astra Zeneca, Ferro Therapeutics, Senti Biosciences, Merck KgA, and Bayer to UCSF; stock ownership in Tatara Therapeutics, Clara Health, BloodQ, Guardant Health, Illumina,… Show more

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Cited by 92 publications
(89 citation statements)
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References 29 publications
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“…Accordingly, isolated previous studies in different cancer types indicated that higher stroma content was associated with longer survival [25] , [26] , [27] , [28] . These and our studies clearly challenge the previous paradigm of the “bad tumour stroma” and support more recent experimental findings that reveal a tumour suppressive role of cancer-associated fibroblasts in pancreatic cancer models [29] , [30] , [31] , indicating that the stroma can also act as a barrier against tumour progression, invasion and development of distant metastasis. The specific evaluation of stroma signalling that inhibit tumour development can provide novel strategies that supplement current armamentarium of cancer therapy.…”
Section: Discussionsupporting
confidence: 91%
“…Accordingly, isolated previous studies in different cancer types indicated that higher stroma content was associated with longer survival [25] , [26] , [27] , [28] . These and our studies clearly challenge the previous paradigm of the “bad tumour stroma” and support more recent experimental findings that reveal a tumour suppressive role of cancer-associated fibroblasts in pancreatic cancer models [29] , [30] , [31] , indicating that the stroma can also act as a barrier against tumour progression, invasion and development of distant metastasis. The specific evaluation of stroma signalling that inhibit tumour development can provide novel strategies that supplement current armamentarium of cancer therapy.…”
Section: Discussionsupporting
confidence: 91%
“…This effect is specific to the cancer cells as the CAFs in the 3D co‐culture did not seem to be overly affected by the combination and this could be due to the increase in cancer stemness of the tumour cells in comparison to the CAFs 18 . This is important to note and a strength of our 3D co‐culture assay as more studies continue to demonstrate that depletion of the stroma does not decrease the progression of the disease 78 . Our efforts are aimed at discovering a therapeutic combination that is efficacious at killing the tumour in the presence of its protective stroma.…”
Section: Discussionmentioning
confidence: 80%
“…Another LOXL inhibitor to show early promise in cancer treatment was the anti-LOXL2 monoclonal mouse antibody AB0023, which was effective in reducing intratumoral collagen density in vivo in a murine model of pancreatic cancer [ 157 ]. Following from this, a humanized version of this antibody, simtuzumab, was developed.…”
Section: Approaches To Target the Lysyl Oxidases Directly And Indimentioning
confidence: 99%