CHFR Methylation for Predicting Taxane Sensitivity in Lung and Esophageal Cancer

CHFR 甲基化用于预测肺癌和食道癌紫杉烷敏感性

基本信息

  • 批准号:
    8116517
  • 负责人:
  • 金额:
    $ 26.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-08-01 至 2013-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Lung and esophageal cancer represent common malignancies which cause the death of >180,000 individuals each year in the United States alone. Currently available chemotherapy both as neoadjuvant treatment and as palliative therapy for advanced disease has had a small but measurable effect on the survival of patients with these diseases. However, while a number of different drugs (for example alkylating agents, platinum compounds, 5FU, and taxanes) are available, no means currently exists for selecting therapy based upon the biology of a patient's individual tumor. We have shown, previously, that DNA hypermethylation associated promoter region silencing of the DNA damage repair gene O6-MGMT, can predict patients sensitive to alkylating agents, and these patients benefit with long-term survival. We now have preliminary data in esophageal cancer patients suggesting that hypermethylation of the checkpoint with forkhead and ring finger domains gene (CHFR) detected by Methylation Specific PCR (MSP) correlates with response to therapy with taxanes and results in prolonged survival of individual patients with CHFR methylation. In the R21 portion of this proposal, we intend to (1) complete a single institution, retrospective trial of neoadjuvant taxane-based therapy in esophageal cancer and extend our analysis to lung cancer patients who also have been treated with neoadjuvant taxanes; (2) detect methylation of CHFR in plasma from patients with esophageal cancer to determine if plasma can be used when tumor tissue is not available; (3) determine the performance characteristics of this assay and compare results between gel-based MSP and real-time MSP for the CHFR gene. In the R33 component of this application, we will validate both our gel-based and real-time tests for CHFR methylation in multi-institutional retrospective studies in lung and esophageal cancer. Then, we intend to apply mainly our real-time assay to prospective studies both in single and multi-institutional settings. These studies, for both neoadjuvant and palliative treatments, will determine the clinical utility of CHFR methylation to predict sensitivity of lung and esophageal cancer to taxanes. They may also provide the basis for targeted use of these agents in other cancer types, including colon, gastric, and head and neck cancer, where CHFR methylation is also frequently observed. Taxanes are a class of chemotherapeutic agents widely used to treat lung and esophageal cancer patients, but many patients do not respond to these drugs. We will further develop a test for CHFR methylation and determine whether CHFR methylation can be used to predict which patients will respond to taxane based chemotherapies.
描述(由申请人提供):肺癌和食管癌是常见的恶性肿瘤,仅在美国每年就造成180万人死亡。目前可用的化疗作为晚期疾病的新辅助治疗和姑息治疗,对这些疾病患者的生存有很小但可测量的影响。然而,虽然有许多不同的药物(例如烷基化剂、铂化合物、5FU和紫杉烷)可用,但目前还没有办法根据患者个体肿瘤的生物学特性来选择治疗方法。我们之前已经证明,DNA超甲基化相关的DNA损伤修复基因O6-MGMT启动子区域沉默可以预测对烷基化剂敏感的患者,这些患者的长期生存受益。我们现在有食管癌患者的初步数据表明,甲基化特异性PCR (MSP)检测到的叉头和环指结构域基因(CHFR)检查点的高甲基化与紫杉烷治疗的反应相关,并导致CHFR甲基化个体患者的生存期延长。在该提案的R21部分,我们打算(1)完成食管癌新辅助紫杉烷治疗的单机构回顾性试验,并将我们的分析扩展到同样接受过新辅助紫杉烷治疗的肺癌患者;(2)检测食管癌患者血浆中CHFR的甲基化,以确定在没有肿瘤组织的情况下血浆是否可以使用;(3)确定该检测的性能特征,并比较凝胶MSP和实时MSP检测CHFR基因的结果。在本申请的R33部分,我们将在肺癌和食管癌的多机构回顾性研究中验证我们基于凝胶和实时的CHFR甲基化测试。然后,我们打算将我们的实时分析主要应用于单一和多机构设置的前瞻性研究。这些新辅助和姑息性治疗的研究将确定CHFR甲基化预测肺癌和食管癌对紫杉烷敏感性的临床应用。它们也可能为在其他类型的癌症中靶向使用这些药物提供基础,包括结肠癌、胃癌和头颈癌,这些癌症也经常观察到CHFR甲基化。紫杉烷类药物是一类广泛用于治疗肺癌和食管癌患者的化疗药物,但许多患者对这些药物没有反应。我们将进一步开发CHFR甲基化测试,并确定CHFR甲基化是否可用于预测哪些患者对紫杉烷类化疗有反应。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Predictive value of CHFR and MLH1 methylation in human gastric cancer.
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JAMES G. HERMAN其他文献

JAMES G. HERMAN的其他文献

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{{ truncateString('JAMES G. HERMAN', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10705801
  • 财政年份:
    2022
  • 资助金额:
    $ 26.25万
  • 项目类别:
Optimizing Ultrasensitive DNA methylation detection for lung cancer and other malignancies
优化肺癌和其他恶性肿瘤的超灵敏 DNA 甲基化检测
  • 批准号:
    10705752
  • 财政年份:
    2022
  • 资助金额:
    $ 26.25万
  • 项目类别:
Core - Biomarker Reference Laboratory (BRL)
核心 - 生物标志物参考实验室 (BRL)
  • 批准号:
    10705806
  • 财政年份:
    2022
  • 资助金额:
    $ 26.25万
  • 项目类别:
Core - Biomarker Development Laboratory (BDL)
核心 - 生物标志物开发实验室 (BDL)
  • 批准号:
    10705802
  • 财政年份:
    2022
  • 资助金额:
    $ 26.25万
  • 项目类别:
Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer
超灵敏检测肿瘤特异性 DNA 甲基化变化以早期发现肺癌
  • 批准号:
    9277030
  • 财政年份:
    2016
  • 资助金额:
    $ 26.25万
  • 项目类别:
Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer
超灵敏检测肿瘤特异性 DNA 甲基化变化以早期发现肺癌
  • 批准号:
    10463037
  • 财政年份:
    2016
  • 资助金额:
    $ 26.25万
  • 项目类别:
Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer
超灵敏检测肿瘤特异性 DNA 甲基化变化以早期发现肺癌
  • 批准号:
    9353351
  • 财政年份:
    2016
  • 资助金额:
    $ 26.25万
  • 项目类别:
CHFR Methylation for Predicting Taxane Sensitivity in Lung and Esophageal Cancer
CHFR 甲基化用于预测肺癌和食道癌紫杉烷敏感性
  • 批准号:
    7667386
  • 财政年份:
    2008
  • 资助金额:
    $ 26.25万
  • 项目类别:
P1: Epigenetic Staging and Therapy for Lung Cancers
P1:肺癌的表观遗传分期和治疗
  • 批准号:
    7567913
  • 财政年份:
    2008
  • 资助金额:
    $ 26.25万
  • 项目类别:
CHFR Methylation for Predicting Taxane Sensitivity in Lung and Esophageal Cancer
CHFR 甲基化用于预测肺癌和食道癌紫杉烷敏感性
  • 批准号:
    7892354
  • 财政年份:
    2008
  • 资助金额:
    $ 26.25万
  • 项目类别:
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