Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma

Nat Commun. 2019 Nov 7;10(1):5076. doi: 10.1038/s41467-019-12846-7.

Dan Su ¹ ² ³, Dadong Zhang ⁴, Jiaoyue Jin ⁵ ⁶, Lisha Ying ⁷ ⁶ ⁸, Miao Han ⁴, Kaiyan Chen ⁹, Bin Li ⁴, Junzhou Wu ⁷ ⁶ ⁸, Zhenghua Xie ⁴, Fanrong Zhang ¹⁰, Yihui Lin ⁴, Guoping Cheng ⁵, Jing-Yu Li ⁴, Minran Huang ⁷ ⁶ ⁸, Jinchao Wang ⁴, Kailai Wang ⁷, Jianjun Zhang ¹¹ ¹², Fugen Li ⁴, Lei Xiong ⁴, Andrew Futreal ¹¹ ¹³, Weimin Mao ¹⁴ ¹⁵ ¹⁶

Affiliations

1 Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China. [email protected].
2 Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China. [email protected].
3 Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China. [email protected].
4 Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai, China.
5 Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
6 Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
7 Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
8 Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
9 Department of Chemotherapy, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
10 Department of Breast Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
11 Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
12 Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
13 Honorary Faculty, Wellcome Trust Sanger Institute, Hinxton, UK.
14 Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China. [email protected].
15 Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China. [email protected].
16 Department of Thoracic Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China. [email protected].

PMID: 31700061 DOI: 10.1038/s41467-019-12846-7

Abstract

Previous studies from the Cancer Cell Line Encyclopedia (CCLE) project have adopted commercial pan-cancer cell line models to identify drug sensitivity biomarkers. However, drug sensitivity biomarkers in esophageal squamous cell carcinoma (ESCC) have not been widely explored. Here, eight patient-derived cell lines (PDCs) are successfully established from 123 patients with ESCC. The mutation profiling of PDCs can partially recapture the tumor tissue actionable mutations from 161 patients with ESCC. Based on these mutations and relative pathways in eight PDCs, 46 targeted drugs are selected for screening. Interestingly, some drug and biomarker relationships are established that were not discovered in the CCLE project. For example, CDKN2A or CDKN2B loss is significantly associated with the sensitivity of CDK4/6 inhibitors. Furthermore, both PDC xenografts and patient-derived xenografts confirm CDKN2A/2B loss as a biomarker predictive of CDK4/6 inhibitor sensitivity. Collectively, patient-derived models could predict targeted drug sensitivity associated with actionable mutations in ESCC.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-50767

Palbociclib

99.96%, CDK4/6 Inhibitor

CDK

Cancer

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