摘要
背景:人表皮生长因子受体2(HER2)的过表达和扩增发生在全部乳腺癌的20%中。 HER2过表达涉及疾病的发生和发展并与预后不良有关。曲妥珠单抗是一种人源化单克隆抗体,是早期和转移性HER2扩增乳腺癌患者的标准HER2靶向治疗药物。曲妥珠单抗在HER2 +转移和辅助治疗中的临床益处显着增加;然而,由于原发性或获得性药物耐药,其对许多患者无效。在过去的十年中,许多研究揭示了许多HER2 +乳腺癌的新分子特征,使我们能够揭示曲妥珠单抗耐药的分子机制,并制定克服治疗耐药性的策略。 目标:在这次审查中,我们全面讨论了目前临床前研究的成果;我们讨论了HER2 +乳腺癌模型中获得性曲妥珠单抗耐药的分子机制以及基于HER2 +乳腺癌分子特征的潜在治疗方法。 结论:加深对HER2 +乳腺癌分子谱的理解可能会导致鉴定新的生物标志物,用于开发诊断方法并改进治疗靶点,以预防和治疗曲妥珠单抗耐药HER2 +乳腺癌。
关键词: HER2 +乳腺癌,靶向治疗,曲妥珠单抗,获得性耐药,细胞系,耐药模型。
Current Medicinal Chemistry
Title:Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models
Volume: 25 Issue: 17
关键词: HER2 +乳腺癌,靶向治疗,曲妥珠单抗,获得性耐药,细胞系,耐药模型。
摘要: Background: Overexpression and amplification of the human epidermal growth factor receptor 2 (HER2) occur in 20% of total breast carcinomas. HER2-overexpression is implicated in disease initiation and progression and associated with poor prognosis. Trastuzumab, a humanized monoclonal antibody, is the standard HER2-targeted therapy for early and metastatic HER2-amplified breast cancer patients. Trastuzumab has significantly increased clinical benefit in HER2+ metastatic and adjuvant settings; however, it is not effective for many patients due to primary or acquired resistance to the drug. During the last decade, many studies have revealed a number of novel molecular traits of HER2+ breast cancer, allowing us to uncover the molecular mechanisms involved in trastuzumab resistance and develop strategies to overcome resistance to therapy.
Objective: In this review, we comprehensively addressed the current achievements in preclinical studies; we discussed molecular mechanisms of acquired trastuzumab resistance in HER2+ breast cancer models and potential therapeutic approaches based on the molecular features for HER2+ breast cancer.
Conclusion: Enhanced understanding of the molecular profiles in HER2+ breast cancer may lead to the identification of novel biomarkers for the development of diagnostic approaches and improvement of therapeutic targets for the prevention and treatment of trastuzumab resistant HER2+ breast cancer.
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Cite this article as:
Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models, Current Medicinal Chemistry 2018; 25 (17) . https://dx.doi.org/10.2174/0929867323666161216144659
DOI https://dx.doi.org/10.2174/0929867323666161216144659 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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