Pathology and Pathophysiology Major, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China.
Mol Divers. 2023 Dec;27(6):2651-2672. doi: 10.1007/s11030-022-10573-8. Epub 2022 Nov 29.
The HER2-positive patients occupy ~ 30% of the total breast cancer patients globally where no prevalent drugs are available to mitigate the frequent metastasis clinically except lapatinib and neratinib. This scarcity reinforced researchers' quest for new medications where natural substances are significantly considered. Valuing the aforementioned issues, this research aimed to study the ERBB2-mediated string networks that work behind the HER2-positive breast cancer formation regarding co-expression, gene regulation, GAMA-receptor-signaling pathway, cellular polarization, and signal inhibition. Following the overexpression, promotor methylation, and survivability profiles of ERBB2, the super docking position of HER2 was identified using the quantum tunneling algorithm. Supramolecular docking was conducted to study the target specificity of EPA and DHA fatty acids followed by a comprehensive molecular dynamic simulation (100 ns) to reveal the RMSD, RMSF, Rg, SASA, H-bonds, and MM/GBSA values. Finally, potential drug targets for EPA and DHA in breast cancer were constructed to determine the drug-protein interactions (DPI) at metabolic stages. Considering the values resulting from the combinational models of the oncoinformatic, pharmacodynamic, and metabolic parameters, long-chain omega-3 fatty acids like EPA and DHA can be considered as potential-targeted therapeutics for HER2-positive breast cancer treatment.
HER2 阳性患者约占全球乳腺癌患者的 30%，除拉帕替尼和奈拉替尼外，临床上尚无有效的药物来减轻其频繁转移。这种稀缺性促使研究人员寻求新的药物，其中天然物质得到了广泛的关注。鉴于上述问题，本研究旨在研究 ERBB2 介导的串扰网络，这些网络在 HER2 阳性乳腺癌的形成中发挥作用，涉及共表达、基因调控、GAMA 受体信号通路、细胞极化和信号抑制。在 ERBB2 的过表达、启动子甲基化和生存能力分析之后，使用量子隧道算法确定了 HER2 的超分子对接位置。进行超分子对接以研究 EPA 和 DHA 脂肪酸的靶标特异性，然后进行全面的分子动力学模拟（100ns），以揭示 RMSD、RMSF、Rg、SASA、氢键和 MM/GBSA 值。最后，构建了 EPA 和 DHA 在乳腺癌中的潜在药物靶标，以确定代谢阶段的药物-蛋白相互作用（DPI）。考虑到肿瘤信息学、药效学和代谢参数组合模型得出的数值，长链 omega-3 脂肪酸如 EPA 和 DHA 可以被认为是 HER2 阳性乳腺癌治疗的潜在靶向治疗药物。
