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。
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
About this article
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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Chemical and Biochemical Basis of Cell-Bone Matrix Interaction in Health and Disease
Current Chemical Biology Microarray-Based Gene Expression Analysis of Hepatocellular Carcinoma
Current Genomics Longevity Pathways (mTOR, SIRT, Insulin/IGF-1) as Key Modulatory Targets on Aging and Neurodegeneration
Current Topics in Medicinal Chemistry Development of Lymphatic Vessels: Tumour Lymphangiogenesis and Lymphatic Invasion
Current Medicinal Chemistry Modifiers of Risk in BRCA1/2 Mutation Carriers
Current Women`s Health Reviews Targeting Water in the Brain: Role of Aquaporin-4 in Ischemic Brain Edema
Current Drug Targets Modulation of Apoptosis: New Opportunities for Drug Discovery to Treat Autoimmune Thyroiditis
Recent Patents on Inflammation & Allergy Drug Discovery Doripenem: A New Addition to the Carbapenem Class of Antimicrobials
Recent Patents on Anti-Infective Drug Discovery Targeting Cellular Proapoptotic Molecules for Developing Anticancer Agents from Marine Sources
Current Drug Targets Probiotics in Intestinal and Non-Intestinal Infectious Diseases – Clinical Evidence
Current Pharmaceutical Design A Review of Preclinical Experiments Toward Targeting M2 Macrophages in Prostate Cancer
Current Drug Targets Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a “Watch-and-Wait” Approach to Cancer
Current Stem Cell Research & Therapy Exploring PLAC1 Structure and Underlying Mechanisms to Design a Derivative Vaccine Against Breast Cancer Progression; <i>In-Silico</i> Study
Current Proteomics Multitargeted Molecular Docking Study of Natural-Derived Alkaloids on Breast Cancer Pathway Components
Current Computer-Aided Drug Design Anti-Inflammatory Actions of the Heme Oxygenase-1 Pathway
Current Pharmaceutical Design Anti-EGFR Binding Nanobody Delivery System to Improve the Diagnosis and Treatment of Solid Tumours
Recent Patents on Anti-Cancer Drug Discovery The Role of Brain Gaseous Transmitters in the Regulation of the Circulatory System
Current Pharmaceutical Biotechnology Targeted Theranostics Against Solid Cancer Using Metal Bond Milk Protein and Aptamers
Current Topics in Medicinal Chemistry Bacteria and Bacterial Toxins as Therapeutic Agents for Solid Tumors
Current Cancer Drug Targets Bioinformatic Application in Proteomic Research on Biomarker Discovery and Drug Target Validation
Current Bioinformatics