Impact of carbamazepine on SMARCA4 (BRG1) expression in colorectal cancer: modulation by KRAS mutation status.

IF 3 3区 医学 Q2 ONCOLOGY
Investigational New Drugs Pub Date : 2024-04-01 Epub Date: 2024-03-06 DOI:10.1007/s10637-024-01418-2
Aaron Shaykevich, Danbee Chae, Isaac Silverman, Jeremy Bassali, Netanel Louloueian, Alexander Siegman, Gargi Bandyopadhyaya, Sanjay Goel, Radhashree Maitra
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引用次数: 0

Abstract

SMARCA4 is a gene traditionally considered a tumor suppressor. Recent research has however found that SMARCA4 likely promotes cancer growth and is a good target for cancer treatment. The drug carbamazepine, an autophagy inducer, was used on colorectal cancer cell lines, HCT1116 and Hke3 (KRAS mutant and wildtype). Our study finds that Carbamazepine affects SMARCA4 levels and that this effect is different depending on the KRAS mutation status. This study analyzes the effect of carbamazepine on early-stage autophagy via ULK1 as well as simulates the docking of carbamazepine on KRAS, depending on the mutation status. Our study highlights the therapeutic uses of carbamazepine on cancer, and we propose that carbamazepine in conjunction with other chemotherapies may prove useful in targeting KRAS-mutated colorectal cancer.

Abstract Image

卡马西平对结直肠癌中 SMARCA4 (BRG1) 表达的影响:受 KRAS 突变状态的调节。
SMARCA4 是一种传统上被认为是肿瘤抑制因子的基因。但最近的研究发现,SMARCA4 可能会促进癌症生长,是治疗癌症的一个很好的靶点。卡马西平是一种自噬诱导剂,被用于结直肠癌细胞系 HCT1116 和 Hke3(KRAS 突变型和野生型)。我们的研究发现,卡马西平会影响 SMARCA4 的水平,而且这种影响因 KRAS 突变状态而异。本研究分析了卡马西平通过 ULK1 对早期自噬的影响,并根据突变状态模拟了卡马西平与 KRAS 的对接。我们的研究强调了卡马西平对癌症的治疗作用,并提出卡马西平与其他化疗药物联用可能会被证明有助于靶向治疗KRAS突变的结直肠癌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
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