Does stanniocalcin predict late breast cancer recurrence, or is it a fish story?

斯钙素是否能预测晚期乳腺癌复发,还是纯属虚构?

基本信息

  • 批准号:
    8692147
  • 负责人:
  • 金额:
    $ 18.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-26 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Advances in the effectiveness of breast cancer screening and treatment have reduced the breast cancer mortality rate over the last decades. These advances come from avoided recurrences, but also from delayed recurrences. The success of chemotherapy, endocrine therapy, and radiation therapy, is typically measured by a reduction in the risk of recurrence in the first five years after breast cancer diagnosis. Many recurrences, however, occur late; that is, more than five years after diagnosis. These recurrences erupt from single dormant cells or micro-metastases where tumor cell growth has been balanced by tumor cell death. How does a single cell, or a small colony of cells, survive for more than five years in a hostile microenvironment that, at least at the outset, often includes hypoxic climates induced by cancer therapies? One likely explanation is that tumors with the capability to recruit stanniocalcin are more likely to survive in this setting and to recur five or more years after diagnosis. Stanniocalcin is a hormone first discovered in bony fish, where it regulates the concentration of calcium at the gills. In humans, nerve cells, fat cells, heart cells, ova, and other long-lived cells recruit stanniocalcin as a survival strategy when they face hypoxic stress, helping them to live in sometimes harsh conditions by uncoupling proton transport from glycosylation in the mitochondria. Preliminary human evidence and in vitro studies show that tumor expression of stanniocalcin is a marker of recurrence risk, and particularly late recurrence risk. We propose, therefore, to use an existing biobank from ~1700 breast cancer patients (841 with recurrence and 841 matched controls) linked to complete clinical data and long-term follow-up for recurrence to investigate whether stanniocalcin expression is a specific marker for late recurrence risk. We will determine whether breast cancer patients with late recurrences were more likely to have had primary tumors that express stanniocalcin than breast cancer patients with early recurrences. We will also determine whether the tumor cells of those with late recurrence are more likely to have retained or acquired the ability to express stanniocalcin than the tumor cells of those with early recurrence. If we find that stanniocalcin is a specific marker for late breast cancer recurrence, we will seek new research support to validate the result in a second breast cancer cohort and in a colorectal cancer cohort, and to investigate drugs to disrupt the pathway. There is no specific marker for late recurrence risk. A marker that predicts when a recurrence will occur, rather than whether a recurrence will occur, would change the clinical paradigm for cancers with substantial late recurrence risk. It would allow personalization of recurrence screening strategies, development of low- toxicity prophylactic therapies that begin when the late recurrence risk rises, and personalization of existing adjuvant therapies with regard to time from diagnosis. This R21 high-risk, high-reward project will initiate a program to identify markers of late recurrence risk and strategies to reduce or ameliorate that risk.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Timothy L. Lash其他文献

Genetic variants in tamoxifen metabolism and early treatment discontinuation among premenopausal breast cancer patients
  • DOI:
    10.1007/s10549-025-07719-1
  • 发表时间:
    2025-05-14
  • 期刊:
  • 影响因子:
    3.000
  • 作者:
    Kirsten M. Woolpert;Thomas P. Ahern;James W. Baurley;Maret L. Maliniak;Per Damkier;Anders Kjærsgaard;Lindsay J. Collin;Stephen Hamilton-Dutoit;Trine Tramm;Bent Ejlertsen;Henrik T. Sørensen;Timothy L. Lash;Deirdre P. Cronin-Fenton
  • 通讯作者:
    Deirdre P. Cronin-Fenton
Real-World Risk of Severe Cytopenias in Multiple Myeloma Patients Sequentially Treated with Immunomodulatory Drugs
  • DOI:
    10.1182/blood-2022-159713
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Julie Barberio;Timothy L. Lash;Ajay K. Nooka;Ashley I. Naimi;Rachel E. Patzer;Christopher Kim
  • 通讯作者:
    Christopher Kim
Anthropometric Measures Among Children and Teens With Classic 46,XX Congenital Adrenal Hyperplasia in Relation to Improvements in Diagnosis and Care
  • DOI:
    10.1016/j.eprac.2024.09.005
  • 发表时间:
    2024-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Courtney McCracken;Oumaima Kaabi;Mackenzie Crawford;Melissa D. Gardner;Darios Getahun;Michael Goodman;Behzad Sorouri Khorashad;Timothy L. Lash;Douglas Roblin;Suma Vupputuri;Rami Yacoub;Phyllis W. Speiser;Peter A. Lee;David E. Sandberg
  • 通讯作者:
    David E. Sandberg
PRESERVATION OF LEFT VENTRICULAR EJECTION FRACTION WITH STATINS DURING RECEIPT OF ANTHRACYCLINE BASED CHEMOTHERAPY
  • DOI:
    10.1016/s0735-1097(12)60987-5
  • 发表时间:
    2012-03-27
  • 期刊:
  • 影响因子:
  • 作者:
    Runyawan Chotenimitkhun;Ralph B. D'Agostino Jr;Julia A. Lawrence;Craig A. Hamilton;Jennifer Jordan;Sujethra Vasu;Timothy L. Lash;W. Hundley
  • 通讯作者:
    W. Hundley
Su052 DEVELOPMENT AND TEMPORAL VALIDATION OF A PREDICTION MODEL FOR RISK-STRATIFIED FIT COLORECTAL CANCER SCREENING
  • DOI:
    10.1016/s0016-5085(21)02128-4
  • 发表时间:
    2021-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Mette K. Thomsen;Lars Pedersen;Rune Erichsen;Timothy L. Lash;Henrik Toft S⊘rensen;Ellen M. Mikkelsen
  • 通讯作者:
    Ellen M. Mikkelsen

Timothy L. Lash的其他文献

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{{ truncateString('Timothy L. Lash', 18)}}的其他基金

Registering Cancer Recurrences in the Georgia Cancer Registry
在佐治亚州癌症登记处登记癌症复发
  • 批准号:
    10556403
  • 财政年份:
    2019
  • 资助金额:
    $ 18.8万
  • 项目类别:
Registering Cancer Recurrences in the Georgia Cancer Registry
在佐治亚州癌症登记处登记癌症复发
  • 批准号:
    10330476
  • 财政年份:
    2019
  • 资助金额:
    $ 18.8万
  • 项目类别:
Improving Reproducibility by Incorporating Uncertainty
通过纳入不确定性来提高再现性
  • 批准号:
    10322751
  • 财政年份:
    2019
  • 资助金额:
    $ 18.8万
  • 项目类别:
Doctoral Student Workshop Co-Sponsored by the Society for Epidemiologic Research
流行病学研究学会联合主办的博士生研讨会
  • 批准号:
    8838485
  • 财政年份:
    2015
  • 资助金额:
    $ 18.8万
  • 项目类别:
Does stanniocalcin predict late breast cancer recurrence, or is it a fish story?
斯钙素是否能预测晚期乳腺癌复发,还是纯属虚构?
  • 批准号:
    8935765
  • 财政年份:
    2014
  • 资助金额:
    $ 18.8万
  • 项目类别:
New and integrated perspectives on modification of tamoxifen effectiveness
关于他莫昔芬有效性修改的新的综合视角
  • 批准号:
    8825461
  • 财政年份:
    2013
  • 资助金额:
    $ 18.8万
  • 项目类别:
New and integrated perspectives on modification of tamoxifen effectiveness
关于他莫昔芬有效性修改的新的综合视角
  • 批准号:
    8439898
  • 财政年份:
    2013
  • 资助金额:
    $ 18.8万
  • 项目类别:
New and integrated perspectives on modification of tamoxifen effectiveness
关于他莫昔芬有效性修改的新的综合视角
  • 批准号:
    8642152
  • 财政年份:
    2013
  • 资助金额:
    $ 18.8万
  • 项目类别:
New and integrated perspectives on modification of tamoxifen effectiveness
关于他莫昔芬有效性修改的新的综合视角
  • 批准号:
    8973797
  • 财政年份:
    2013
  • 资助金额:
    $ 18.8万
  • 项目类别:
Cancer Prevention and Control
癌症预防与控制
  • 批准号:
    10595769
  • 财政年份:
    2009
  • 资助金额:
    $ 18.8万
  • 项目类别:

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