title: CDK4/6 inhibitor suppresses gastric cancer with CDKN2A mutation.
abstract: OBJECTIVE
  Gastric cancer is a major health problem and current treatment lacks lasting effect. Targeted therapy for gastric cancer with specific genetic background is in urgent need.
  
  
  METHODS
  We have studied The Cancer Genomic Atlas (TCGA) and The Genomics of Drug Sensitivity in Cancer (GDSC) databases to reveal genes with high frequency of mutation and possible sensitive compound against such gene mutation. In vitro studies were conducted to validate the in silico findings.
  
  
  RESULTS
  CDKN2A is frequently mutated in gastric cancer, revealed in TCGA database. CDK4/6 inhibitor PD-0332991 was sensitive in cancer cells with CDKN2A mutation, revealed in GDSC database. In vitro studies showed that PD-0332991 could selectively inhibit proliferation of gastric cancer cell with CDKN2A mutation. PD-0332991 could also inhibit cell invasion, migration, and colony formation of gastric cancer cell with CDKN2A mutation. PD-0332991 induced cell cycle arrest but not apoptosis. PD-0332991 inhibited xenograft gastric cancer mouse model.
  
  
  CONCLUSIONS
  Gastric cancer with CDKN2A mutation is sensitive to CDK4/6 inhibitor. PD-0332991 is a potential therapeutic agent for gastric cancer.
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Nali
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital Ningbo 315040, Zhejiang, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhejiang Provincial People's Hospital 158 Shangtang Rd, Hangzhou 310041, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
keywords: CDK4/6; CDKN2A; Gastric cancer; cell cycle