A pancreatic cancer organoid platform identifies an inhibitor specific to mutant KRAS

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成果类型：

期刊论文

作者：

Duan, Xiaohua;Zhang, Tuo;Feng, Lingling;de Silva, Neranjan;Greenspun, Benjamin;...

通讯作者：

Evans, Todd;Chen, Shuibing;Pan, FC;Chen, SB

作者机构：

[Chen, Shuibing; Pan, Fong Cheng; Feng, Lingling; Evans, Todd; Pan, FC; Duan, Xiaohua; de Silva, Neranjan; Greenspun, Benjamin; Chandwani, Rohit] Weill Cornell Med, Dept Surg, 1300 York Ave, New York, NY 10065 USA.

[Chen, Shuibing; Evans, Todd; Duan, Xiaohua; Greenspun, Benjamin] Weill Cornell Med, Ctr Genom Hlth, 1300 York Ave, New York, NY 10065 USA.

[Zhang, Tuo] Weill Cornell Med, Genom Resources Core Facil, New York, NY 10065 USA.

[Feng, Lingling] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol CCNU, Minist Educ, Wuhan 430079, Hubei, Peoples R China.

[Wang, Xing; Moyer, Jenna; Elemento, Olivier; Martin, M. Laura] Weill Cornell Med, Caryl & Israel Englander Inst Precis Med, New York, NY USA.

通讯机构：

[Evans, T; Chen, SB; Chen, SB ; Pan, FC ] W

Weill Cornell Med, Dept Surg, 1300 York Ave, New York, NY 10065 USA.

Weill Cornell Med, Ctr Genom Hlth, 1300 York Ave, New York, NY 10065 USA.

语种：

英文

关键词：

KRAS;SREBP2;cholesterol biosynthesis;colon cancer organoids;lung cancer organoids;orthotopic transplantation;pancreatic organoid;perhexiline maleate;targeted therapy

期刊：

Cell Stem Cell

ISSN：

1934-5909

年：

2024

卷：

期：

页码：

71-88.e8

DOI：

10.1016/j.stem.2023.11.011

基金类别：

Weill Cornell Medicine; Department of Surgery Pancreatic Cancer Initiative; National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) [R01DK130454, R01DK119667, R01DK119667-02S1, U01 DK127777]; National Cancer Institute [NCI R01CA204228, R01DK060694]; Tri-Institutional Stem Cell Initiative [Tri-Sci 202005]; Department of Surgery, Weill Cornell Medicine; Irma Hirschl Trust Research Award Scholar

机构署名：

本校为第一机构

院系归属：

化学学院

摘要：

KRAS mutations, mainly G12D and G12V, are found in more than 90% of pancreatic ductal adenocarcinoma (PDAC) cases. The success of drugs targeting KRAS(G12C) suggests the potential for drugs specifically targeting these alternative PDAC-associated KRAS mutations. Here, we report a high-throughput drug-screening platform using a series of isogenic murine pancreatic organoids that are wild type (WT) or contain common PDAC driver mutations, representing both classical and basal PDAC phenotypes. We screened over 6,000 compounds and identified perhexiline maleate, which can inhibit the growth and in...

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A pancreatic cancer organoid platform identifies an inhibitor specific to mutant KRAS

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