Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

被引：321

作者：

Driehuis, Else ^{[1
,2
,3
]}

van Hoeck, Arne ^{[1
,4
]}

Moore, Kat ^{[5
]}

Kolders, Sigrid ^{[1
,2
,3
]}

Francies, Hayley E. ^{[6
]}

Gulersonmez, M. Can ^{[7
]}

Stigter, Edwin C. A. ^{[7
]}

Burgering, Boudewijn ^{[7
]}

Geurts, Veerle ^{[1
,2
,3
]}

Gracanin, Ana ^{[8
]}

Bounova, Gergana ^{[5
]}

Morsink, Folkert H. ^{[9
]}

Vries, Robert ^{[8
]}

Boj, Sylvia ^{[8
]}

van Es, Johan ^{[1
,2
,3
]}

Offerhaus, G. Johan A. ^{[9
]}

Kranenburg, Onno ^{[10
]}

Garnett, Mathew J. ^{[6
]}

Wessels, Lodewyk ^{[5
]}

Cuppen, Edwin ^{[1
,4
,11
,12
]}

Brosens, Lodewijk A. A. ^{[9
]}

Clevers, Hans ^{[1
,2
,3
,13
]}

机构：

[1] Univ Med Ctr Utrecht, Oncode Inst, NL-3584 CX Utrecht, Netherlands

[2] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, Ctr Mol Med, NL-3584 CG Utrecht, Netherlands

[5] Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

[6] Wellcome Sanger Inst, Hinxton CB10 1SA, England

[7] Univ Med Ctr Utrecht, Oncode Inst, Ctr Mol Med, Dept Mol Canc Res, NL-3584 CM Utrecht, Netherlands

[8] Hubrecht Organoid Technol, NL-3584 CM Utrecht, Netherlands

[9] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CM Utrecht, Netherlands

[10] Utrecht Med Ctr Utrecht, Utrecht Platform Organoid Technol, NL-3584 CM Utrecht, Netherlands

[11] Hartwig Med Fdn, NL-1098 XH Amsterdam, Netherlands

[12] Univ Med Ctr Utrecht, Ctr Personalized Canc Treatment, NL-3584 CM Utrecht, Netherlands

[13] Princess Maxima Ctr, NL-3584 CS Utrecht, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2019年 / 116卷 / 52期

基金：

英国惠康基金;

关键词：

pancreatic cancer; organoids; personalized medicine; cancer; biobank; PHOSPHORYLASE; ACCUMULATION; METHYLATION; DEPENDENCE; BIOBANK; MODELS; GENES; PRMT5;

D O I：

10.1073/pnas.1911273116

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

引用

页码：26580 / 26590

页数：11

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