摘要
背景:抗血管生成药物舒尼替尼从未被用作为未经治疗的乳腺癌患者的单一药物。 目的:我们的目的是在局部未经治疗或可手术的的晚期乳腺癌显示舒尼替尼单独的和联用多烯紫杉醇的活性,揭示其反应的机制。 方法:患者接受舒尼替尼的前期窗口治疗,然后四个周期的舒尼替尼联合多烯紫杉醇。根据标准的临床参数,磁共振成像,正电子发射断层扫描,标准的病理学特性,分子病理学和基因表达谱来评价其反应、耐药和毒性。 结果:共纳入十二例患者。我们检测未经治疗的乳腺癌在前期窗口对舒尼替尼的原发耐药性,证明四例患者无反应。在手术中,五例患者在乳腺和腋窝有存活的肿瘤,四例患者仅在乳腺有存活的肿瘤细胞和三例由于不可接受毒性被排除研究未被评价。早期功能成像在预测反应中是有用的。没有临床的全面反应。早期反应者和无反应者之间的肿瘤基因表达谱数据的比较,使我们能够确定无反应者的血管内皮生长因子和血管生成途径的上调。具体来说,我们检测到肿瘤抵抗单药舒尼替尼有对缺氧的转录反应,显示几种HIF1α靶基因的过度表达。 结论:本文报告单药舒尼替尼治疗未经治疗的局部乳腺癌患者,我们发现了舒尼替尼原发性耐药可能通过缺氧反应基因上调介导的的证据。
关键词: 舒尼替尼,新辅助治疗,乳腺癌、耐药,缺氧,表达谱。
图形摘要
Current Cancer Drug Targets
Title:Does Hypoxic Response Mediate Primary Resistance to Sunitinib in Untreated Locally Advanced Breast Cancer?
Volume: 17 Issue: 1
Author(s): Sofia Braga, Joana Cardoso, Saudade Andre, Margarida Brito, Pedro Sanchez, Lurdes Orvalho, Lucilia Salgado, Sergio Dias and Jose B. Pereira-Leal, Jose Luis Passos-Coelho
Affiliation:
关键词: 舒尼替尼,新辅助治疗,乳腺癌、耐药,缺氧,表达谱。
摘要: Background: The antiangiogenic drug sunitinib has never been evaluated as single agent in untreated breast cancer patients.
Objective: We aimed to characterize the activity of sunitinib, alone and with docetaxel, in untreated locally advanced or operable breast cancer and to uncover the mechanisms of response. Method: Patients were treated with an upfront window of sunitinib followed by four cycles of sunitinib plus docetaxel. Response, resistance and toxicity were evaluated according to standard clinical parameters, magnetic resonance imaging, positron emission tomography, standard pathology characterization, molecular pathology and gene expression profiling. Results: Twelve patients were included. We detected primary resistance to sunitinib in the upfront window in untreated breast cancer, as evidenced by four non-responding patients. At surgery, five patients had viable tumor in the breast and axilla, four had viable tumor cells in the breast alone and three were taken off study and thus not evaluated, due to unacceptable toxicity. Early functional imaging was useful in predicting response. There were no clinical complete responses. Comparison of tumor gene expression profiling data between early responders and non-responders allowed us to identify the up-regulation of VEGF and angiogenic pathways in non-responders. Specifically, in tumors resistant to single-agent sunitinib we detected a transcriptional response to hypoxia characterized by over-expression of several HIF1α target genes. Conclusion: In this report of single-agent sunitinib treatment in untreated localized breast cancer patients, we found evidence of primary resistance to sunitinib, likely mediated by up-regulation of hypoxia responsive genes.Export Options
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Cite this article as:
Sofia Braga, Joana Cardoso, Saudade Andre, Margarida Brito, Pedro Sanchez, Lurdes Orvalho, Lucilia Salgado, Sergio Dias and Jose B. Pereira-Leal, Jose Luis Passos-Coelho , Does Hypoxic Response Mediate Primary Resistance to Sunitinib in Untreated Locally Advanced Breast Cancer?, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666161025114914
DOI https://dx.doi.org/10.2174/1568009616666161025114914 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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