PROGNOSTIC MARKERS FOR ASSESSMENT OF TREATMENT EFFICACY OF MELANOMA

描述(申请人提供)：管理中的主要问题之一 恶性黑色素瘤预测疾病的进展过程 切除原发肿瘤。我们的主要假设是分子标记 可用于分析肿瘤和血液，作为预测疾病的替代物 进展和结果，以及治疗效果提前很久 临床病理事件。恶性黑色素瘤的进展发生在 导致进行性疾病的多个遗传异常的积累 遗传不稳定。为了将检测和预测价值转化为 要有效地进行这些变化，必须对来自 明确的回顾和前瞻性临床试验。验证 分子结果将使更好的疾病分层和管理 恶性黑素瘤。在之前的资助期间，我们开发了多标记RT-PCR 鉴定血液预后分子标志物(PMM)和 证明它们可以作为亚临床的潜在替代品。 疾病进展，并预测疾病复发。我们将继续 在这项提案中，开发新的针对血液的信息丰富的PMM。我们的假设是 包括黑色素瘤相关抗原在内的PMM的数量水平 (MAAS)与影响肿瘤的细胞生理因素 黑色素瘤的进展/转移也可作为 疾病转归和主动特异性免疫疗法(疫苗)的疗效。 我们的假设是，原发和转移性黑色素瘤的DNA标志物也可以 被用作PMM。我们已经鉴定了几个DNA标记，它们已经显示出 潜在的临床病理应用价值。在此次续订中，我们将重点关注 评估成对的原发/转移性黑色素瘤发生不同类型的 PMMS补充血液RT-PCR检测与疾病进展相关 和结果，以及治疗失败。 该项目的目标如下：1)开发和评估新的 用于评估黑色素瘤患者肿瘤和血液的mRNA PMM；2)开发和 黑色素瘤DNA标志物作为预后指标的评估 疾病进展和结果；以及3)临床和 RNA和DNA分子标记在恶性黑色素瘤中的病理意义 患者进入多中心PMCV第三阶段临床试验。目标 将利用JWCI的大量黑色素瘤患者转介和 全面跟进，为开发和评估PMM提供资源。这个 AIMS还将利用随机多中心疫苗试验的 存档和预期收集的标本以验证PMM。 恶性黑色素瘤不同阶段分子标志物的鉴定 疾病进展将使我们能够开发出一种“适用的”分子 为管理决策提供帮助的进度模型。

DESCRIPTION (provided by applicant): One of the major problems in managing malignant melanoma is predicting the course of disease progression after removal of the primary tumor. Our main hypothesis is that molecular markers can be used for analysis of tumors and blood as surrogates to predict disease progression and outcome, and treatment efficacy well in advance of clinicopathological events. Malignant melanoma progression occurs from accumulation of multiple genetic aberrations that result in progressive genetic instability. In order to translate the detection and prognostic value of these changes efficiently, analysis must be conducted on specimens from well-defined retrospective and prospective clinical trials. Validation of the molecular results will allow better disease stratification and management of malignant melanoma. In the previous grant period we developed multimarker RTPCR assays to identify blood prognostic molecular markers (PMMs) and demonstrated that they could be useful as potential surrogates of subclinical disease progression, and to predict disease recurrence. We will continue to develop new informative PMMs for blood in this proposal. Our hypothesis is that quantitative levels of PMMs which include melanoma-associated antigens (MAAs) and cellular physiologic factors influencing tumor progression/metastasis in melanoma tumors can also be used as surrogates of disease outcome and the efficacy of active-specific immunotherapy (vaccine). Our hypothesis is that DNA markers in primary and metastatic melanoma can also be used as PMMs. We have identified several DNA markers that have shown potential clinicopathological utility. In this renewal we will focus on assessing paired primary/metastatic melanomas to develop different types of PMMs to complement the blood RT-PCR assay as correlates to disease progression and outcome, and treatment failure. The Aims of the project are as follows: 1) Development and assessment of new mRNA PMMs for assessing melanoma patients' tumor and blood; 2) Development and assessment of DNA markers in melanoma tumors as prognostic indicators of disease progression and outcome; and 3) Validation of the clinical and pathological utility of RNA and DNA molecular markers in melanomas from patients entered in the multicenter PMCV Phase III clinical trial. The Aims will take advantage of the JWCI's large melanoma patient referral and comprehensive follow up to provide resources to develop and assess PMMs. The Aims will also take advantage of the randomized multicenter vaccine trial's archived and prospectively collected specimens to validate the PMMs. Identification of molecular markers for melanoma at different stages of disease progression will allow us to develop an "applicable" molecular progression model to aid in management decisions.