Multiplex Biomarkers for Prostate Cancer

前列腺癌的多重生物标志物

• 批准号: 7538459
• 负责人: SUSAN C WRIGHT
• 金额: $ 19.88万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-12 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538459
• 关键词: Accounting; Biological Assay; Biological Markers; Biopsy; Blood Tests; Blood specimen; Cancer Detection; Cancer Etiology; Cells; Cessation of life; Classification; Clinical; Detection; Diagnosis; Diagnostic Neoplasm Staging; Diagnostic tests; Enzyme-Linked Immunosorbent Assay; Lead; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical; Methodology; Mutation; Outcome; Pathology; Patients; Phase; Polymerase Chain Reaction; Procedures; Prophylactic treatment; Prostate-Specific Antigen; Proteins; Proteomics; Public Health; Range; Rate; Reagent; Risk; Screening for cancer; Second Primary Neoplasms; Sensitivity and Specificity; Serum; Staging; Statistically Significant; Technology; Testing; Time; United States; base; clinically relevant; male; men; tumorigenesis

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.

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，也是导致男性癌症死亡的第二大原因，占男性所有新发癌症的 1/3，每年估计有 232,090 例新发病例（Jemal， 2005）。前列腺癌检测的主要手段是通过血液检测是否存在前列腺特异性抗原（PSA）。尽管 PSA 检测有助于早期发现癌症，但恶性肿瘤与 PSA 之间的相关性并不强。 PSA 检测呈阳性意味着患者有 25% 的机会患癌症，这导致 75% 的男性进行不必要的活检（Barry，2001）。相反，阴性结果实际上可能会漏掉大多数癌症（Hernandez，2004）。显然，需要更准确的诊断测试来消除不需要的治疗，并更好地识别确实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生物标志物，这些生物标志物可以在前列腺癌的诊断中补充甚至替代 PSA（Bradford，2006）。鉴于癌症发现得越早，临床结果就越好，并且肿瘤发生涉及细胞内的多种遗传变化，因此量化多种低丰度癌症相关蛋白的诊断测试是最理想的。此类测试往往比单目标测定更准确，并且其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），但基于 ELISA 的传统技术的敏感性可能会限制其在临床检测中的使用。为了满足这一需求，我们正在开发 Prostaplex(tm)，这是一种基于多重实时免疫 PCR (MRI-PCR) 的新型检测方法，可检测 10 种前列腺癌生物标志物的存在。我们的方法灵敏、可重复、在大动态范围内有效，并且能够多重检测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、更准确地检测和分期前列腺癌。更早、更准确的检测将减少不必要的活检，减少不需要的医疗程序，提高实际患有癌症的患者的治愈率，并为尚未患癌症的高危患者提供更好的预防和随访。公共健康相关性：前列腺癌是美国男性最常见的恶性肿瘤，也是导致男性癌症死亡的第二大原因，占男性所有新发癌症的 1/3，每年估计有 232,090 例新发病例（Jemal，2005 年）。前列腺癌检测的主要手段是通过血液检测是否存在前列腺特异性抗原（PSA）。尽管 PSA 检测有助于早期发现癌症，但恶性肿瘤与 PSA 之间的相关性并不强。 PSA 检测呈阳性意味着患者有 25% 的机会患癌症，这导致 75% 的男性进行不必要的活检（Barry，2001）。相反，阴性结果实际上可能会漏掉大多数癌症（Hernandez，2004）。显然，需要更准确的诊断测试来消除不需要的治疗，并更好地识别确实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生物标志物，这些生物标志物可以在前列腺癌的诊断中补充甚至替代 PSA（Bradford，2006）。鉴于癌症发现得越早，临床结果就越好，并且肿瘤发生涉及细胞内的多种遗传变化，因此量化多种低丰度癌症相关蛋白的诊断测试是最理想的。此类测试往往比单目标测定更准确，并且其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），但基于 ELISA 的传统技术的敏感性可能会限制其在临床检测中的使用。为了满足这一需求，我们正在开发 Prostaplex(tm)，这是一种基于多重实时免疫 PCR (MRI-PCR) 的新型检测方法，可检测 10 种前列腺癌生物标志物的存在。我们的方法灵敏、可重复、在大动态范围内有效，并且能够多重检测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、更准确地检测和分期前列腺癌。更早、更准确的检测将减少不必要的活检，减少不需要的医疗程序，提高实际患有癌症的患者的治愈率，并为尚未患癌症的高危患者提供更好的预防和随访。