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

Hyun Joo Bae, Sun Kyoung Kang, Woo Sun Kwon, Inhye Jeong, Sejung Park, Tae Soo Kim, Kyoo Hyun Kim, Hyunki Kim, Hei Cheul Jeong, Hyun Cheol Chung, Sun Young Rha

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1 Citation (Scopus)

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.

Original languageEnglish
Article number114320
JournalBiochemical Pharmacology
Volume183
DOIs
Publication statusPublished - 2021 Jan

Bibliographical note

Funding Information:
Abemaciclib was provided by Eli Lilly and Company (Lilly Corporate Center, Indianapolis, Indiana). This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1A2B5B02001452) and also supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0018).

Publisher Copyright:
© 2020 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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