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

机译：P16甲基化是一种潜在的预测标记，用于胃癌中的胃癌敏感性

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摘要

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.
机译：细胞周期控制通常在胃癌（GC）中被破坏，使其成为有吸引力的治疗目标。 ABEMACICLIB是一种特定的CDK4 / 6抑制剂，已被证明可以改善激素受体阳性晚期乳腺癌治疗效果;然而，其潜在的治疗价值和预测标志物尚未在GC中揭示。在本研究中，我们研究了ABEMACICLIB使用代表来自癌症基因组地图集的定义分子亚型的临床前GC模型的功效。在这些49个GC细胞系中，Epstein-Barr病毒（EBV）和高微卫星不稳定性（MSI-H）型细胞系为P16甲基化和对ABEMAciclib敏感;此外，还发现基因组稳定（GS）和染色体不稳定性（CIN）型细胞系具有p16甲基化和完整的RB。此外，我们发现GC甲基化的GC患者经常呈现出差的预后。总的来说，这些数据为临床试验提供了临床试验的基础，以评估GC中的ABEMACIBIB的治疗效果，并表明P16甲基化可用作预测标记，以鉴定可能从基于ABEMICIB的疗法中受益的GC患者。

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