PSA Peptidase Activity (PPA): A New Biomarker for Prostate Cancer Aggressiveness

描述（由申请人提供）：本SBIR II期提案的主要目标是确定存在于各种生理样本中的新型前列腺癌（PCa）非侵袭性生物标志物的临床价值，例如前列腺液（PF）、前列腺分泌物（EPS）或按摩后尿液样本（PMU）。一旦在本研究中得到统计学验证（n=841），这种“非侵袭性”生物标志物将成为可靠和创新的预后检测的基础，它将补充国家综合癌症网络（NCCN）已经建立的积极监测的现行临床指南6.更高的筛查率加上改进的检测方法，导致接受筛查的男性人数出现有争议的激增。前列腺活检和随后的治疗。7在确诊PCa后，医生和患者通常选择临床干预，尽管有证据表明干预并不总是必要的，特别是对于低风险、非侵袭性癌症。4这些干预的负面副作用，可能包括尿失禁，阳痿和肠功能障碍使PCa过度诊断的争议持续存在，过度治疗归因于筛查的增加。10最近来自美国预防服务工作组（USPSTF）和美国泌尿外科协会（AUA）的建议，停止常规PSA筛查，然而，这些减少筛查的建议引起了人们对“漏诊”癌症死亡率潜在上升的担忧。 最近的学术研究表明，PSA的酶活性同种型在肿瘤侵袭和转移中起着重要作用。11在I期和后续研究中，Ohmx发现前列腺液和前列腺分泌物中PSA肽酶活性（PPA）水平与疾病分期成反比，使得患有非侵袭性PCa的患者与患有更侵袭性疾病的患者相比平均具有显著增加的PPA水平。5显著地，初步结果表明，许多（在初始研究人群n=100中为22%）诊断为非侵袭性PCa的患者可以避免或延迟根治性前列腺癌切除术。 Ohmx提出了一种范式转变，补充了筛查技术，并提供了一种预后测试，可以直接帮助改善治疗决策。一个非侵略性的测试结果减少了不必要的临床干预的数量，从而保持患者的生活质量，同时降低整体医疗保健成本。这项创新的检测将提高非侵袭性癌症的鉴别能力，并结合最近的NCCN指南（基于活检分期、Gleason评分、PSA结果和患者年龄）6，将提高患者对主动监测的接受程度和对延迟治疗的风险分层的信心。

DESCRIPTION (provided by applicant): The principal goal of this SBIR Phase II proposal is to establish the clinical value of a novel prostate cancer (PCa) non-aggressiveness biomarker present in various physiological samples e.g. Prostatic Fluids, (PFs), Expressed Prostatic Secretions, (EPS), or Post-Massage Urine samples, (PMUs). Once statistically validated in this study (n=841), this "non-aggressiveness" biomarker will be the basis of a reliable and innovative prognostic test that will complement the current clinical guidelines for active surveillance alread established by the National Comprehensive Cancer Network (NCCN).6 Greater screening rates in conjunction with improved detection methods have resulted in a controversial upsurge in the number of men undergoing prostate biopsy and subsequent treatments.7 Upon diagnosis of PCa, physicians and patients typically choose clinical interventions, despite evidence that intervention is not always warranted, especially for low-risk, non-aggressive cancers.4 The negative side effects of these interventions, which may include, incontinence, impotence and bowel dysfunction are perpetuating the controversy of PCa overdiagnosis & overtreatment attributed to increased screening.10 Recent recommendations from the U.S. Preventative Services Task Force (USPSTF) and the American Urology , Association (AUA), to discontinue routine PSA screening, have further fueled the controversy.8 9 However, these recommendations for reducing screening have created concern about the potential uptick in mortality from "missed" cancers. Recent academic studies suggest that the enzymatically active isoform of PSA plays a significant role in tumor invasion and metastasis.11 In Phase I and subsequent studies, Ohmx found the level of PSA Peptidase Activity (PPA) in prostatic fluid and expressed prostatic secretions to be inversely proportional to disease stage, such that patients with the non-aggressive PCa have on average significantly increased PPA levels compared to those with more aggressive disease.5 Significantly, preliminary results suggest many (22% in an initial study population n=100) of the diagnosed patients with non-aggressive PCa could have averted or delayed radical prostatectomy. Ohmx is proposing a paradigm shift that complements screening techniques and provides a prognostic test that can directly aid in the refinement of treatment decisions. A non-aggressive test result reduces the number of unnecessary clinical interventions, thereby maintaining the patient's quality of life, while reducing overall healthcare costs. This innovative test will enhance the differentiation of non-aggressive cancer, and in conjunction with recent NCCN guidelines (based on biopsy stage, Gleason score, PSA results and the age of the patient) 6 will increase patients' acceptance of active surveillance and confidence in risk stratification for delaying treatment.