Exploring synergistic therapeutic potential of Erlotinib and artemisinin in non-small cell lung Cancer (NSCLC) using pharmacological networking and mathematical modeling

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2026-04-01 Epub Date: 2026-02-09 DOI:10.1016/j.cca.2026.120890

Faiqa Suleman , Tasadduq Khan , Salah A. Alshehade , Muhammad Ali , Hafiz Muhammad Irfan , Amir Shahzad , Raghdaa Hamdan Al Zarzour , Shahid Rasool

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引用次数: 0

Abstract

Background

Lung cancer remains one of the most aggressive malignancies worldwide, with non-small cell lung cancer (NSCLC) constituting the major subtype. Resistance to targeted therapies poses a persistent challenge in precision medicine, emphasizing the need for more effective therapeutic strategies.

Methods

This study explored the synergistic potential between Erlotinib (ERL) and Artemisinin (ART), a phytochemical compound, using network pharmacology, differential gene expression (DGE) analysis, and mathematical models of potential drug synergy and conceptual interaction modeling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to identify potential key molecular targets and biological pathways involved in NSCLC treatment response.

Results

Key potential targets such as HSP90AA1, SRC, ABL1, and JAK2 were identified, with significant modulation of the PI3K-Akt, Rap1, Ras, and VEGF signaling pathways contributing to therapeutic outcomes. Exploratory synergy modeling using the Bliss, Loewe, and simplified ZIP models revealed potential synergistic trends between Erlotinib and Artemisinin, indicating enhanced anti-tumor potential compared to Erlotinib monotherapy. Mathematical evaluation of drug conceptual interaction modeling provided further insights into Predicted drug–target interactions and pathway-level complementarity.

Conclusions

This integrative computational and mathematical approach elucidates the putative mechanistic interplay between drugs and phytochemicals, highlighting the potential of Artemisinin–Erlotinib (ART-ERL) combination therapy in overcoming drug resistance in NSCLC. The findings offer a promising framework for rational design of future combination strategies to improve clinical outcomes in lung cancer therapy.

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利用药理学网络和数学模型探索厄洛替尼和青蒿素在非小细胞肺癌（NSCLC）中的协同治疗潜力。

背景：肺癌仍然是世界范围内最具侵袭性的恶性肿瘤之一，非小细胞肺癌（NSCLC）是主要亚型。对靶向治疗的耐药性对精准医学构成了持续的挑战，强调需要更有效的治疗策略。方法：利用网络药理学、差异基因表达（DGE）分析、潜在药物协同作用数学模型和概念相互作用模型，探讨厄洛替尼（ERL）与植物化合物青蒿素（ART）的协同作用潜力。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）途径富集分析，确定参与NSCLC治疗反应的潜在关键分子靶点和生物学途径。结果：HSP90AA1、SRC、ABL1和JAK2等关键潜在靶点被确定，PI3K-Akt、Rap1、Ras和VEGF信号通路的显著调节有助于治疗结果。使用Bliss、Loewe和简化ZIP模型的探索性协同建模揭示了厄洛替尼和青蒿素之间潜在的协同趋势，表明与厄洛替尼单药相比，抗肿瘤潜力增强。药物概念相互作用模型的数学评估为预测药物-靶标相互作用和途径水平的互补性提供了进一步的见解。结论：这种综合的计算和数学方法阐明了药物和植物化学物质之间可能的机制相互作用，突出了青蒿素-厄洛替尼（ART-ERL）联合治疗在克服NSCLC耐药方面的潜力。这些发现为合理设计未来的联合策略以改善肺癌治疗的临床结果提供了一个有希望的框架。

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

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.