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

doi:10.1016/j.bcp.2020.114320

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (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 language	English
Article number	114320
Journal	Biochemical Pharmacology
Volume	183
DOIs	https://doi.org/10.1016/j.bcp.2020.114320
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bcp.2020.114320

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title = "p16 methylation is a potential predictive marker for abemaciclib sensitivity in gastric cancer",

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.",

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

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: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

month = jan,

doi = "10.1016/j.bcp.2020.114320",

language = "English",

volume = "183",

journal = "Biochemical Pharmacology",

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T1 - p16 methylation is a potential predictive marker for abemaciclib sensitivity in gastric cancer

AU - Bae, Hyun Joo

AU - Kang, Sun Kyoung

AU - Kwon, Woo Sun

AU - Jeong, Inhye

AU - Park, Sejung

AU - Kim, Tae Soo

AU - Kim, Kyoo Hyun

AU - Kim, Hyunki

AU - Jeong, Hei Cheul

AU - Chung, Hyun Cheol

AU - Rha, Sun Young

N1 - 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.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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