Multiplex Biomarkers for Prostate Cancer

描述（由申请人提供）：前列腺癌是美国男性中最常见的恶性肿瘤，也是癌症死亡的第二大原因，占男性所有新发癌症的三分之一，估计每年有232,090例新发病例（Jemal, 2005）。前列腺癌检测的主要方法是血液检测前列腺特异性抗原（PSA）的存在。虽然PSA检测可以早期发现癌症，但恶性肿瘤与PSA之间的相关性并不强。PSA检测呈阳性表明患者有25%的机会患癌症，这导致75%的男性进行不必要的活组织检查（Barry, 2001）。相反，阴性结果实际上可能会错过大多数癌症（Hernandez, 2004）。显然，需要更准确的诊断测试来消除不必要的治疗，并更好地确定需要治疗的患者子集。蛋白质组学分析已经发现了许多候选的生物标志物，这些生物标志物可以补充甚至取代前列腺癌诊断中的PSA （Bradford, 2006）。考虑到越早发现癌症，临床结果越好，并且肿瘤发生涉及细胞内的多种遗传变化，最需要的是量化多种低丰度癌症相关蛋白的诊断测试。这类试验往往比单一目标测定法更准确，而且它们的灵敏度提供了非常早期和准确检测的可能性。幸运的是，已经发现了前列腺癌的低丰度生物标志物（Bradford, 2006），但是基于ELISA的传统技术的敏感性可能限制了它们在临床分析中的应用。为了满足这一需求，我们正在开发Prostaplex(tm)，这是一种新的基于多路实时免疫PCR （MRI-PCR）的检测方法，可检测10种前列腺癌生物标志物的存在。我们的方法是敏感的，可重复的，在大动态范围内有效，并且能够复用到数十甚至数百种癌症生物标志物。我们预计Prostaplex（tm）将比目前可用的检测方法更早、更准确地检测前列腺癌并进行分期。更早、更准确的检测将减少不必要的活组织检查，减少不必要的医疗程序，提高实际患有癌症的患者的治愈率，并为尚未发展为癌症的高危患者提供更好的预防和随访。公共卫生相关性：前列腺癌是美国男性最常见的恶性肿瘤，也是癌症死亡的第二大原因，占男性所有新发癌症的三分之一，估计每年有232,090例新发病例（Jemal, 2005）。前列腺癌检测的主要方法是血液检测前列腺特异性抗原（PSA）的存在。虽然PSA检测可以早期发现癌症，但恶性肿瘤与PSA之间的相关性并不强。PSA检测呈阳性表明患者有25%的机会患癌症，这导致75%的男性进行不必要的活组织检查（Barry, 2001）。相反，阴性结果实际上可能会错过大多数癌症（Hernandez, 2004）。显然，需要更准确的诊断测试来消除不必要的治疗，并更好地确定需要治疗的患者子集。蛋白质组学分析已经发现了许多候选的生物标志物，这些生物标志物可以补充甚至取代前列腺癌诊断中的PSA （Bradford, 2006）。考虑到越早发现癌症，临床结果越好，并且肿瘤发生涉及细胞内的多种遗传变化，最需要的是量化多种低丰度癌症相关蛋白的诊断测试。这类试验往往比单一目标测定法更准确，而且它们的灵敏度提供了非常早期和准确检测的可能性。幸运的是，已经发现了前列腺癌的低丰度生物标志物（Bradford, 2006），但是基于ELISA的传统技术的敏感性可能限制了它们在临床分析中的应用。为了满足这一需求，我们正在开发Prostaplex(tm)，这是一种新的基于多路实时免疫PCR （MRI-PCR）的检测方法，可检测10种前列腺癌生物标志物的存在。我们的方法是敏感的，可重复的，在大动态范围内有效，并且能够复用到数十甚至数百种癌症生物标志物。我们预计Prostaplex（tm）将比目前可用的检测方法更早、更准确地检测前列腺癌并进行分期。更早、更准确的检测将减少不必要的活组织检查，减少不必要的医疗程序，提高实际患有癌症的患者的治愈率，并为尚未发展为癌症的高危患者提供更好的预防和随访。

DESCRIPTION (provided by applicant): Prostate cancer is the most common malignancy and second-leading cause of cancer deaths among males in the United States, accounting for 1/3 of all new cancers in males with an estimated 232,090 new cases yearly (Jemal, 2005). The mainstay of prostate cancer detection is a blood test for the presence of prostate-specific antigen (PSA). Although testing for PSA has led to earlier cancer detection, the correlation between malignancy and PSA is not strong. A positive test for PSA signifies that a patient has a 25% chance for cancer, which causes 75% of men to have unnecessary biopsies (Barry, 2001). Conversely, a negative result may actually miss the majority of cancers (Hernandez, 2004). Clearly, more accurate diagnostic tests are needed to eliminate unneeded treatment as well as better identify the subset of patients that do require treatment. Proteomic analysis has resulted in the discovery of many candidate biomarkers that may supplement or even replace PSA in the diagnosis of prostate cancer (Bradford, 2006). Given that the earlier cancer is detected the better the clinical outcome, and that tumorigenesis involves multiple genetic changes within cells, diagnostic tests that quantify multiple low-abundance cancer-associated proteins are most desirable. Such tests tend to be more accurate than single target assays and their sensitivity affords the possibility of very early and accurate detection. Fortunately, low abundance biomarkers for prostate cancer have been discovered (Bradford, 2006), but the sensitivity of conventional technology based on ELISA may limit their use in clinical assays. To meet this need, we are developing Prostaplex(tm), a new Multiplexed Real-time Immuno PCR (MRI-PCR) based assay that detects the presence of 10 prostate cancer biomarkers. Our methodology is sensitive, reproducible, valid over a large dynamic range, and capable of being multiplexed to dozens or even hundreds of cancer biomarkers. We anticipate that Prostaplex(tm) will result in earlier, more accurate prostate cancer detection and staging than currently available assays. Earlier, more accurate detection will lead to fewer unneeded biopsies, fewer medical procedures for those who do not require them, better cure rates for patients that actually have cancer, and better prophylaxis and follow ups for at-risk patients who have not yet developed cancer. PUBLIC HEALTH RELEVANCE:Prostate cancer is the most common malignancy and second-leading cause of cancer deaths among males in the United States, accounting for 1/3 of all new cancers in males with an estimated 232,090 new cases yearly (Jemal, 2005). The mainstay of prostate cancer detection is a blood test for the presence of prostate-specific antigen (PSA). Although testing for PSA has led to earlier cancer detection, the correlation between malignancy and PSA is not strong. A positive test for PSA signifies that a patient has a 25% chance for cancer, which causes 75% of men to have unnecessary biopsies (Barry, 2001). Conversely, a negative result may actually miss the majority of cancers (Hernandez, 2004). Clearly, more accurate diagnostic tests are needed to eliminate unneeded treatment as well as better identify the subset of patients that do require treatment. Proteomic analysis has resulted in the discovery of many candidate biomarkers that may supplement or even replace PSA in the diagnosis of prostate cancer (Bradford, 2006). Given that the earlier cancer is detected the better the clinical outcome, and that tumorigenesis involves multiple genetic changes within cells, diagnostic tests that quantify multiple low-abundance cancer-associated proteins are most desirable. Such tests tend to be more accurate than single target assays and their sensitivity affords the possibility of very early and accurate detection. Fortunately, low abundance biomarkers for prostate cancer have been discovered (Bradford, 2006), but the sensitivity of conventional technology based on ELISA may limit their use in clinical assays. To meet this need, we are developing Prostaplex(tm), a new Multiplexed Real-time Immuno PCR (MRI-PCR) based assay that detects the presence of 10 prostate cancer biomarkers. Our methodology is sensitive, reproducible, valid over a large dynamic range, and capable of being multiplexed to dozens or even hundreds of cancer biomarkers. We anticipate that Prostaplex(tm) will result in earlier, more accurate prostate cancer detection and staging than currently available assays. Earlier, more accurate detection will lead to fewer unneeded biopsies, fewer medical procedures for those who do not require them, better cure rates for patients that actually have cancer, and better prophylaxis and follow ups for at-risk patients who have not yet developed cancer.