Utility of serum and Tissue Biomarkers for Predicting Response to Androgen Depriv

大多数患有前列腺癌的男性现在被诊断为具有低风险的肿瘤， mortality.这类患者最常采用根治性乳房切除术或外照射治疗 放疗（EBRT），然后定期进行血清PSA评估。大多数男人都有 PSA确定性治疗后在诊断性活检后数月或数年出现（EBRT病例）或 根治性乳房切除术（在手术的情况下）。有些会有临床上明显的局部复发， 临床上可检测到的转移，但许多人将没有其他证据复发前列腺癌以外， 升高或可检测到PSA。一些临床医生使用PSA“倍增时间”来确定 这些人需要辅助激素消融，局部放射治疗，或简单的观察。我们 假设额外的生物标志物将有助于预测哪些男性在确定性治疗后PSA升高 会从额外的治疗中获益 由于许多男性在接受明确治疗后数月或数年内出现PSA升高， 在其他地方，最重要的生物标志物将是那些可以在标本上进行的生物标志物， 同时且容易获得，即血清或血浆。项目1的主要目标是开发 潜在的血清生物标志物，这将有助于在这种情况下的患者的管理。然而，在这方面， 在诊断时预测男性的预后是当前翻译的重要方向。 前列腺癌的研究项目1的第二个目标是了解组织中的改变是否 初次诊断时的生物标志物与后来的PSA进展和进一步的PSA进展相关。 系统进展。 为了实现这些重点目标，项目1旨在谨慎地利用患者人群 马约诊所前列腺癌实践的资源以及马约诊所实验室和临床的专业知识 科学家具体目标1将发现与前列腺癌进展相关的组织生物标志物， 明确治疗后PSA升高的患者。使用特定目标1、特定目标2的数据 将开发血清生物标志物，类似地预测PSA升高患者的前列腺癌进展 经过明确的治疗。为了开始将这些关联转化为临床实践，具体目标3 将进行一项II期临床试验，以确定暂时性雄激素剥夺对患有 主要确定性治疗后PSA升高，并确定雄激素消融反应的相互作用 血清和组织生物标志物改变该项目将产生新的生物标志物面板， 用于大量重要的前列腺癌男性患者的临床管理。

The majority of men with prostate cancer are now diagnosed with tumors with a low risk of causespecific mortality. Such men are most frequently treated with radical prostatectomy or external beam radiotherapy (EBRT) and are followed by regular serum PSA evaluations thereafter. Most men with a rising PSA post-definitive therapy present several months or years after diagnostic biopsy (in the case of EBRT) or radical prostatectomy (in the case of surgery). Some will have clinically obvious local recurrence, have clinically detectable metastasis, but many will have no other evidence of recurrent prostate cancer other than a rising or detectable PSA. The PSA "doubling time" has been used by some clinicians to determine which of these men deserve adjuvant hormonal ablation, local radiation therapy, or simple observation. We hypothesize that additional biomarkers will help predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Since many men present with a rising PSA months or years after receiving their definitive therapy elsewhere, the most important biomarkers will be those that can be performed on a specimen that is contemporaneously and easily available, i.e. serum or plasma. The primary goal of Project 1 is to develop potential serum biomarkers that will assist in the management of patients in this situation. However, predicting the prognosis of men at the time of diagnosis is an important direction of current translational prostate cancer research. The secondary goal of Project 1 is to learn if the alterations in the tissue biomarkers at the time of initial diagnosis are associated with later PSA progression and with further systemic progression. To accomplish these focused goals, Project 1 is designed to carefully utilize the patient population resources of the Mayo Clinic prostate cancer practice and the expertise of Mayo Clinic laboratory and clinical scientists. Specific Aim 1 will discover tissue biomarkers associated with prostate cancer progression in patients with rising PSA following definitive treatment. Using the data from Specific Aim 1, Specific Aim 2 will develop serum biomarkers that similarly predict prostate cancer progression in patients with rising PSA following definitive treatment. To begin to translate these associations into clinical practice, Specific Aim 3 will conduct a phase II clinical trial to determine the effect of temporary androgen deprivation in men with a rising PSA after primary definitive therapy and determine the interaction of response to androgen ablation with serum and tissue biomarker alterations. This project will generate new biomarker panels that will be used in the clinical management of a large and important population of men with prostate cancer.