NF-kB oscillation profiles decode response to anti-EGFR monoclonal antibodies

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

SLAS Discovery Pub Date : 2025-01-31 DOI:10.1016/j.slasd.2025.100219

Donatella Romaniello , Lorenzo Dall'Olio , Martina Mazzeschi , Anna Francia , Federica Pagano , Valerio Gelfo , Gabriele D'Uva , Enrico Giampieri , Mattia Lauriola

{"title":"NF-kB oscillation profiles decode response to anti-EGFR monoclonal antibodies","authors":"Donatella Romaniello , Lorenzo Dall'Olio , Martina Mazzeschi , Anna Francia , Federica Pagano , Valerio Gelfo , Gabriele D'Uva , Enrico Giampieri , Mattia Lauriola","doi":"10.1016/j.slasd.2025.100219","DOIUrl":null,"url":null,"abstract":"<div><div>A direct connection between an inflammatory environment and cancer has been extensively proven over the years. We previously reported that the presence of interleukin 1 (IL-1) is responsible for the lack of response to monoclonal antibody targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC).</div><div>Considering the driver role of NF-kB in controlling the expression of IL-1, herein, we investigate the dynamics of the oscillatory profile of the NF-kB response to monoclonal antibody, on the background of an inflammatory environment. NF-kB is a typical transcription factor that displays intrinsic oscillatory behavior, whose biological relevance in term for example of decoding response to monoclonal antibodies, remains unclear.</div><div>Using live cell luciferase techniques, we recorded NF-kB activity over time in response to cetuximab (CTX) alone or in combination with IL-1 cytokines. Our results revealed an additive effect of these two agents on NF-kB activation, which was specific to CTX responsive cells. In contrast, CTX resistant cells did not display a significant change in the NF-kB profile under the IL-1 plus CTX combination. These results suggest an immediate interactive crosstalk between IL-1 and EGFR in the activation of NF-kB signaling pathway, which may lay the basis for the development of drug tolerant persister cells (DTP), leading to CTX resistance.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100219"},"PeriodicalIF":2.7000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SLAS Discovery","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2472555225000127","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

A direct connection between an inflammatory environment and cancer has been extensively proven over the years. We previously reported that the presence of interleukin 1 (IL-1) is responsible for the lack of response to monoclonal antibody targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC).

Considering the driver role of NF-kB in controlling the expression of IL-1, herein, we investigate the dynamics of the oscillatory profile of the NF-kB response to monoclonal antibody, on the background of an inflammatory environment. NF-kB is a typical transcription factor that displays intrinsic oscillatory behavior, whose biological relevance in term for example of decoding response to monoclonal antibodies, remains unclear.

Using live cell luciferase techniques, we recorded NF-kB activity over time in response to cetuximab (CTX) alone or in combination with IL-1 cytokines. Our results revealed an additive effect of these two agents on NF-kB activation, which was specific to CTX responsive cells. In contrast, CTX resistant cells did not display a significant change in the NF-kB profile under the IL-1 plus CTX combination. These results suggest an immediate interactive crosstalk between IL-1 and EGFR in the activation of NF-kB signaling pathway, which may lay the basis for the development of drug tolerant persister cells (DTP), leading to CTX resistance.

查看原文本刊更多论文

NF-κB振荡谱解码对抗egfr单克隆抗体的应答。

多年来，炎症环境和癌症之间的直接联系已被广泛证实。我们之前报道过白介素1 （IL-1）的存在是导致结直肠癌（CRC）对靶向EGFR的单克隆抗体缺乏反应的原因。考虑到NF-κB在控制IL-1表达中的驱动作用，本文在炎症环境的背景下，研究了NF-κB对单克隆抗体反应的振荡谱动力学。NF-kB是一种典型的转录因子，表现出固有的振荡行为，其生物学相关性，例如对单克隆抗体的解码反应，尚不清楚。使用活细胞荧光素酶技术，我们记录了西妥昔单抗（CTX）单独或与IL-1细胞因子联合作用时NF-κB随时间的活性。我们的研究结果显示，这两种药物对NF-κB活化具有叠加效应，这是CTX应答细胞所特有的。相比之下，在IL-1 + CTX联合作用下，CTX耐药细胞的NF-κB谱没有明显变化。这些结果表明，在NF-κB信号通路的激活过程中，IL-1和EGFR之间存在直接的相互作用串扰，这可能为耐药持久细胞（DTP）的发展奠定基础，从而导致CTX耐药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

SLAS Discovery Chemistry-Analytical Chemistry

CiteScore

7.00

自引率

3.20%

发文量

审稿时长

39 days

期刊介绍： Advancing Life Sciences R&D: SLAS Discovery reports how scientists develop and utilize novel technologies and/or approaches to provide and characterize chemical and biological tools to understand and treat human disease. SLAS Discovery is a peer-reviewed journal that publishes scientific reports that enable and improve target validation, evaluate current drug discovery technologies, provide novel research tools, and incorporate research approaches that enhance depth of knowledge and drug discovery success. SLAS Discovery emphasizes scientific and technical advances in target identification/validation (including chemical probes, RNA silencing, gene editing technologies); biomarker discovery; assay development; virtual, medium- or high-throughput screening (biochemical and biological, biophysical, phenotypic, toxicological, ADME); lead generation/optimization; chemical biology; and informatics (data analysis, image analysis, statistics, bio- and chemo-informatics). Review articles on target biology, new paradigms in drug discovery and advances in drug discovery technologies. SLAS Discovery is of particular interest to those involved in analytical chemistry, applied microbiology, automation, biochemistry, bioengineering, biomedical optics, biotechnology, bioinformatics, cell biology, DNA science and technology, genetics, information technology, medicinal chemistry, molecular biology, natural products chemistry, organic chemistry, pharmacology, spectroscopy, and toxicology. SLAS Discovery is a member of the Committee on Publication Ethics (COPE) and was published previously (1996-2016) as the Journal of Biomolecular Screening (JBS).