Predicting Melanoma Response to BAY 43-9006/Chemotherapy
预测黑色素瘤对 BAY 43-9006/化疗的反应
基本信息
- 批准号:7078609
- 负责人:
- 金额:$ 28.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-06-15 至 2009-05-31
- 项目状态:已结题
- 来源:
- 关键词:angiogenesisantineoplasticsapoptosisbiomarkercancer registry /resourcecarboplatinclinical researchcombination chemotherapyhigh throughput technologyhuman tissuekinase inhibitormelanomametastasismicroarray technologymitogen activated protein kinaseneoplasm /cancer chemotherapyneoplasm /cancer pharmacologyneoplastic growthpaclitaxelpharmacogeneticsprotein quantitation /detection
项目摘要
DESCRIPTION (provided by applicant): Mortality from melanoma is rising due to the increase in incidence and lack of effective therapy once the disease has metastasized. One of the most promising new therapies is carboplatin (C), paclitaxel (T) and BAY43-9006 (B), which revealed very high response rates with unusually long mean time to disease progression in a Phase l/ll trial in metastatic melanoma. ECOG is opening a randomized trial comparing CT to CTB, called E2603. The precise mechanism of BAY 43-9006 is unknown, and response to CTB appears not to be associated with B-RAF activating mutations. We hypothesize that (a) mechanisms other than B-RAF inhibition are involved in the activity of this combination of drugs and (b) CTB will benefit only a subset of melanoma patients. We strive to find markers that predict response in the individual patient in order to ultimately treat only those patients that are likely to respond. We will screen selected markers for association with response to therapy, and perform comprehensive analysis on the best predictive markers. We will use a novel, objective, automated quantitative method of tissue microarray analysis (AQUA) to evaluate expression of proteins from three groups that are known to be induced by these drugs; the MARK pathway, apoptotic pathways and pro-angiogenic proteins. We will start with rigorous validation of antibodies to a subset of these proteins, followed by initial evaluation on tumors from 50 patients treated with CTB in the Phase l/ll study. Markers with differences in expression between responders and non-responders will be further evaluated on 300 archival melanoma specimens and 300 benign nevi to assess prevalence of markers expression in metastatic melanomas. Concurrently, specimens from patients enrolled in E2603 will be prospectively collected. Using AQUA on tissue microarrays, we will study differences in marker expression between responders and non-responders on both treatment arms, with the goal of developing an assay to specifically predict response to CTB. We will assess individual markers as well as panels of markers.
描述(由申请人提供):由于发病率的增加和疾病转移后缺乏有效治疗,黑色素瘤的死亡率正在上升。最有希望的新疗法之一是卡铂(C)、紫杉醇(T)和BAY 43 -9006(B),其在转移性黑素瘤的I/II期试验中显示非常高的响应率和异常长的平均疾病进展时间。ECOG正在开展一项比较CT与CTB的随机试验,称为E2603。BAY 43-9006的确切机制尚不清楚,对CTB的反应似乎与B-RAF激活突变无关。我们假设(a)B-RAF抑制以外的机制参与了这种药物组合的活性,(B)CT B仅对一部分黑色素瘤患者有益。我们努力寻找预测个体患者反应的标志物,以便最终只治疗那些可能有反应的患者。我们将筛选选定的与治疗反应相关的标志物,并对最佳预测标志物进行全面分析。我们将使用一种新的,客观的,自动化的定量方法组织微阵列分析(AQUA),以评估蛋白质的表达,从三个组是已知的诱导这些药物; MARK途径,凋亡途径和促血管生成蛋白。我们将从针对这些蛋白质的子集的抗体的严格验证开始,然后对来自I/II期研究中用CTB治疗的50名患者的肿瘤进行初步评价。将在300例存档黑素瘤标本和300例良性痣中进一步评价应答者和非应答者之间表达差异的标志物,以评估转移性黑素瘤中标志物表达的患病率。同时,将前瞻性采集入组E2603的患者的标本。在组织微阵列上使用AQUA,我们将研究两个治疗组中应答者和非应答者之间标志物表达的差异,目的是开发一种检测方法来特异性预测对CTB的应答。我们将评估单个标记以及标记组。
项目成果
期刊论文数量(0)
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Harriet M. Kluger其他文献
Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma
- DOI:
10.1186/s40425-019-0675-0 - 发表时间:
2019-07-23 - 期刊:
- 影响因子:10.600
- 作者:
Pok Fai Wong;Wei Wei;Swati Gupta;James W. Smithy;Daniel Zelterman;Harriet M. Kluger;David L. Rimm - 通讯作者:
David L. Rimm
Evolving Immunotherapy Approaches for Renal Cell Carcinoma
- DOI:
10.1007/s11912-016-0542-9 - 发表时间:
2016-07-30 - 期刊:
- 影响因子:5.000
- 作者:
Susanna A. Curtis;Justine V. Cohen;Harriet M. Kluger - 通讯作者:
Harriet M. Kluger
Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT).
卡博替尼 (XL184) 在转移性黑色素瘤中的活性:II 期随机停药试验 (RDT) 的结果。
- DOI:
10.1200/jco.2012.30.15_suppl.8531 - 发表时间:
2012 - 期刊:
- 影响因子:45.3
- 作者:
Michael S. Gordon;Harriet M. Kluger;G. Shapiro;R. Kurzrock;G. Edelman;Thomas A. Samuel;A. Moussa;D. Ramies;A. D. Laird;F. Schimmoller;Xiao;A. Daud - 通讯作者:
A. Daud
Clonal determinants of organotropism and survival in metastatic uveal melanoma
转移性葡萄膜黑色素瘤器官趋向性和生存的克隆决定因素
- DOI:
10.1101/2024.05.14.593919 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Bailey S.C.L. Jones;Patrick C. Demkowicz;Mitchelle Matesva;Renelle Pointdujour Lim;John H. Sinard;Antonietta Bacchiocchi;Ruth Halaban;M. Bosenberg;Mario Sznol;Harriet M. Kluger;Mathieu F. Bakhoum - 通讯作者:
Mathieu F. Bakhoum
Correction to: Incidence and characteristics of metastatic intracranial lesions in stage III and IV melanoma: a single institute retrospective analysis
- DOI:
10.1007/s11060-021-03825-4 - 发表时间:
2021-08-17 - 期刊:
- 影响因子:3.100
- 作者:
Mani Ratnesh S. Sandhu;Veronica L. Chiang;Thuy Tran;James B. Yu;Sarah A. Weiss;Sarah B. Goldberg;Mariam S. Aboian;Harriet M. Kluger;Amit Mahajan - 通讯作者:
Amit Mahajan
Harriet M. Kluger的其他文献
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{{ truncateString('Harriet M. Kluger', 18)}}的其他基金
Dual-isotope SPECT imaging and immunophenotyping of immune cells to determine response to immunotherapy
双同位素 SPECT 成像和免疫细胞免疫表型分析以确定对免疫治疗的反应
- 批准号:
10590408 - 财政年份:2023
- 资助金额:
$ 28.38万 - 项目类别:
The Yale Cancer Center Calabresi Immuno-Oncology Training Program (IOTP)
耶鲁大学癌症中心卡拉布雷西免疫肿瘤学培训计划 (IOTP)
- 批准号:
9899739 - 财政年份:2018
- 资助金额:
$ 28.38万 - 项目类别:
YALE CANCER CENTER CALABRESI IMMUNO-ONCOLOGY TRAINING PROGRAM
耶鲁大学癌症中心卡拉布雷西免疫肿瘤学培训计划
- 批准号:
10646793 - 财政年份:2018
- 资助金额:
$ 28.38万 - 项目类别:
Yale SPORE in Lung Cancer Career Enhancement Program
耶鲁 SPORE 肺癌职业提升计划
- 批准号:
10203858 - 财政年份:2015
- 资助金额:
$ 28.38万 - 项目类别:
A research and training program for junior clinicians in treating metastatic mela
初级临床医生治疗转移性黄斑变性的研究和培训计划
- 批准号:
8581535 - 财政年份:2013
- 资助金额:
$ 28.38万 - 项目类别:
A research and training program for junior clinicians in treating metastatic mela
初级临床医生治疗转移性黄斑变性的研究和培训计划
- 批准号:
8692684 - 财政年份:2013
- 资助金额:
$ 28.38万 - 项目类别:
A research and training program for junior clinicians in treating metastatic mela
初级临床医生治疗转移性黄斑变性的研究和培训计划
- 批准号:
9279067 - 财政年份:2013
- 资助金额:
$ 28.38万 - 项目类别:
Models to Predict Prognosis and Benefit from Adjuvant Therapy in Renal Cell Carci
预测肾细胞癌预后和辅助治疗获益的模型
- 批准号:
8613470 - 财政年份:2011
- 资助金额:
$ 28.38万 - 项目类别:
Models to predict prognosis and benefit from adjuvant therapy in renal cell carci
预测肾细胞癌预后和辅助治疗获益的模型
- 批准号:
8085276 - 财政年份:2011
- 资助金额:
$ 28.38万 - 项目类别:
Models to predict prognosis and benefit from adjuvant therapy in renal cell carci
预测肾细胞癌预后和辅助治疗获益的模型
- 批准号:
8236884 - 财政年份:2011
- 资助金额:
$ 28.38万 - 项目类别:
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