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p16 methylation is a potential predictive marker for abemaciclib sensitivity in gastric cancer

Authors
 Bae, Hyun Joo  ;  Kang, Sun Kyoung  ;  Kwon, Woo Sun  ;  Jeong, Inhye  ;  Park, Sejung  ;  Kim, Tae Soo  ;  Kim, Kyoo Hyun  ;  Kim, Hyunki  ;  Jeong, Hei-Cheul  ;  Chung, Hyun Cheol  ;  Rha, Sun Young 
Citation
 BIOCHEMICAL PHARMACOLOGY, Vol.183, 2021-01 
Journal Title
 BIOCHEMICAL PHARMACOLOGY 
ISSN
 0006-2952 
Issue Date
2021-01
Keywords
Abemaciclib ; Gastric cancer ; P16 ; Methylation ; Cell cycle
Abstract
Cell cycle control is often disrupted in gastric cancer (GC), making it an attractive therapeutic target. Abemaciclib is a specific CDK4/6 inhibitor that has been shown to improve treatment efficacy in hormone receptor positive advanced breast cancer; however, its potential therapeutic value and predictive markers have not yet been revealed in GC. In this study, we investigated the efficacy of abemaciclib using preclinical GC models representing defined molecular subtypes from The Cancer Genome Atlas. In these 49 GC cell lines, Epstein-Barr virus (EBV) and high microsatellite instability (MSI-H)-type cell lines were p16 methylated and sensitive to abemaciclib; further, genomically stable (GS), and chromosomal instability (CIN)-type cell lines with p16 methylation and intact Rb were also found to be responsive. In addition, we found that GC patients with p16 methylation often displayed a poor prognosis. Collectively, these data provide a foundation for clinical trials to assess the therapeutic efficacy of abemaciclib in GC and suggest that p16 methylation could be used as a predictive marker to identify patients with GC who may benefit from abemaciclib-based therapies.
DOI
10.1016/j.bcp.2020.114320
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선)
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Jung, In Hye(정인혜) ORCID logo https://orcid.org/0000-0003-0553-0310
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181875
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