SERUM CYT-MAA AS AN EARLY MARKER OF RESPONSE TO THERAPY IN RESECTED MELANOMA

描述（由申请人提供）：我们的最终目标是开发一种血清学标志物，可以提供切除的黑色素瘤治疗反应的早期指征。目前，判断对辅助治疗的反应的唯一方法是等待疾病复发，因此迫切需要这种标记物。到那时，治疗癌症的最佳机会可能已经失去。我们将研究血清CYT-MAA（一种与黑色素瘤相关的抗原）水平是否可以提供这一信息。该提议基于非常有希望的初步数据，该数据表明CYT-MAA存在于许多切除的黑素瘤患者的血清中，辅助治疗可以降低该抗原的血清水平，并且这与改善的临床结果相关。在R21阶段，我们将：1）优化和2）验证我们开发的用于测量血清CYT-MAA的灵敏定量夹心ELISA。在R33阶段，我们将应用优化的检测方法，正式检查其作为黑色素瘤预后标志物和治疗反应早期标志物的价值。要解决的问题包括：1）不同阶段切除的黑色素瘤患者和年龄匹配的无黑色素瘤个体中血清CYT-MAA的发生率和水平。2)该标志物的存在和/或水平与临床结果之间的相关性。3)切除的黑色素瘤患者接受治疗后血清CYT-MAA水平发生的变化以及这些变化是否与临床结局相关。4)血清CYT-MAA是否比其他标志物（如LDH和S100 B）更早或更有用地指示治疗反应。该提案的优点是：a）它解决了黑素瘤护理中严重未满足的需求，B）试验数据表明CYT-MAA似乎是对治疗的早期反应的敏感标志物，c）获得含有在用各种药剂治疗黑素瘤期间连续收集的样本以及相关临床结果数据的大型血清库，（d）经验丰富的调查人员之间的多机构合作，在开展这项工作所需的技能方面具有互补经验。这项工作的成功完成将为切除的黑色素瘤提供疾病进展和/或治疗反应的替代标志物，这将通过允许更快速地识别将受益于早期引入替代治疗的无反应患者来改善临床决策。

DESCRIPTION (provided by applicant): Our ultimate goal is to develop a serological marker that can provide an early indication of response to therapy in resected melanoma. There is a critical need for such a marker, as presently the only way to judge response to adjuvant therapy is to wait for disease recurrence. By that time, the best chance to treat the cancer may have been lost. We will investigate whether serum levels of CYT-MAA, an antigen associated with melanoma, can provide this information. The proposal is based on very promising pilot data indicating CYT-MAA is present in serum of many patients with resected melanoma, that adjuvant therapy can decrease serum levels of this antigen, and that this is associated with an improved clinical outcome. In the R21 phase, we will: 1) Optimize and 2) validate a sensitive and quantitative sandwich ELISA we have developed to measure serum CYT-MAA. In the R33 phase, we will apply the optimized assay to formally examine its value as a prognostic marker of melanoma and as an early marker of response to therapy. The questions to be addressed include: 1) The incidence and level of serum CYT-MAA in patients with different stages of resected melanoma and age- matched individuals without melanoma. 2) The correlation between presence and/or level of this marker and clinical outcome. 3) The changes that occur in serum levels of CYT-MAA with treatment in patients with resected melanoma and whether these correlate with clinical outcome. 4) Whether serum CYT-MAA provides an earlier or more useful indication of response to therapy than other markers such as LDH and S100B. The strengths of the proposal are: a) It addresses a serious unmet need in the care of melanoma, b) pilot data indicates CYT-MAA appears to be a sensitive marker of early response to therapy, c) access to large sera banks containing specimens collected serially during therapy of melanoma with a variety of agents together with linked clinical outcome data, d) multi-institutional collaborations between very experienced investigators with complementary experience in the skills required to conduct this work. Successful completion of this work will provide a surrogate marker of disease progression and/or response to therapy in resected melanoma that will improve clinical decision making by permitting more rapid identification of unresponsive patients who would benefit from early introduction of alternate therapy.