Mayo Clinic Prospective Resource for Biomarker Validation and Early Detection of Pancreatic Cancer

梅奥诊所生物标志物验证和胰腺癌早期检测的前瞻性资源

• 批准号: 10696167
• 负责人: Shounak Majumder
• 金额: $ 78.17万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696167
• 关键词: Address; Age; Algorithms; Biological Assay; Biological Markers; Biological Specimen Banks; Biometry; Blinded; Blood; Blood Proteins; Blood specimen; CA-19-9 Antigen; Cancer Detection; Cancer Etiology; Cancer-Predisposing Gene; Centers of Research Excellence; Cessation of life; Characteristics; Clinic; Collection; Cyst Fluid; DNA Markers; DNA Methylation; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Discrimination; Disease; Early Diagnosis; Early identification; Eligibility Determination; Epidemiology; Evaluation; Familial pancreatic cancer; Family; Family history of; Gastroenterology; General Population; Genetic; Genetic Predisposition to Disease; Germ-Line Mutation; Goals; Grant; Guidelines; Incidence; Individual; Infrastructure; Knowledge; Leadership; Longitudinal cohort; Malignant Neoplasms; Malignant neoplasm of pancreas; Mass Spectrum Analysis; Measurable; Methodology; Methods; Non-Malignant; Pancreas; Pancreatic Cyst; Pancreatic Diseases; Pancreatic Ductal Adenocarcinoma; Participant; Patients; Pennsylvania; Performance; Phase; Plasma; Population; Procedures; Proteins; Protocols documentation; Race; Recommendation; Recording of previous events; Resources; Risk; Risk Factors; Sampling; Screening for cancer; Smoking; Standardization; Survival Rate; Symptoms; THBS2 gene; Testing; Time trend; Tissues; United States; Universities; Validation; biobank; biomarker development; biomarker panel; biomarker validation; blood product; clinical effect; clinical translation; cohort; design; diagnostic accuracy; disorder control; early detection biomarkers; early onset; experience; high risk; high risk population; improved; individual patient; innovation; kindred; member; multidisciplinary; mutational status; new technology; novel; novel marker; novel strategies; pancreatic ductal adenocarcinoma model; patient variability; phase 2 designs; phase 2 study; phase 2 testing; phase 3 study; phase 3 testing; prospective; protein biomarkers; recruit; sample collection; screening; sex; stem cell model; tool

Pancreatic ductal adenocarcinoma (PDAC) is typically detected at late stage due to absence of a cancer screening strategy, with concomitant poor survival rates. Detection of PDAC at an early stage positively impacts survival, and currently screening in eligible high-risk individuals (HRIs) defined by family history and germline mutation status is considered best practice. The overall goal of this proposal is to use knowledge gained during the last grant period to considerably enhance our ability to develop and validate the diagnostic performance of new blood protein and methylated DNA (MDM) biomarkers for early detection of PDAC, using prospective specimen collection and retrospective blinded evaluation (PRoBE) compliant methods. We hypothesize that a combination of proteins, MDMs, and CA19-9 will accurately identify early stage PDAC in HRIs. We will assess the performance characteristics of our approaches in early stage and pre-diagnostic phase of PDAC and identify approaches that are optimized for clinical translation as an early detection tool using HRIs. For over two decades, Mayo Clinic’s prospective biospecimen resources have accrued, using standardized high-quality procedures, well-annotated biospecimens from thousands of PDAC patients including those with germline mutations in pancreas cancer susceptibility genes, high risk members in familial pancreatic cancer kindreds, patients with high-risk pancreatic conditions, and healthy controls. We have also launched the PCDC Signature Protocols at our center. Among those at risk with biospecimens who we have followed longitudinally over two decades, incident PDAC cases have developed, enabling us to utilize novel approaches to address the challenges and better design PRoBE phase 3 studies. Based on our findings in the last grant period, we now focus on tailoring samples for PRoBE phase 2 studies and characterizing performance to improve phase 3 studies. Our approach will allow us to assess, for example, variability in biomarker expression for intended use HRI settings, and temporality of biomarker expression to improve the ability to detect early onset PDAC. Our Specific Aims are to: 1) Accrue formal biospecimen sets from blood sample products and pancreatic cyst fluid suitable for PCDC biomarker studies; 2) Leverage our past knowledge and experience to develop new biomarker panels using tailored phase 2 designs and incorporating covariates to refine detection (age, sex, race, smoking, personal history of diabetes mellitus, symptoms at diagnosis) to optimize detection; and 3) Evaluate needed performance parameters that will inform the design of a successful phase 3 study for PDAC in a surveillance setting of HRIs. Our multidisciplinary team is committed to continue its leadership and contribution to the PCDC organization to advance the early detection of pancreatic cancer. Our project leverages existing infrastructures and biospecimen banks of pancreatic cancer and other pancreatic diseases at Mayo Clinic and University of Pennsylvania, and it will extend new prospective collections of blood and pancreatic cyst fluid from patients, contributing to PCDC Signature Protocol cohorts and a PCDC central biorepository.

胰腺导管腺癌（PDAC）通常在晚期发现，因为没有癌症

项目成果

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants.

具有致病性或可能致病性种系变异的胰腺导管腺癌患者的一级亲属患综合征相关癌症的风险。

• DOI: 10.1001/jamaoncol.2023.0806
• 发表时间: 2023
• 期刊: JAMA oncology
• 影响因子: 28.4
• 作者: Chen,Xuan;Meyer,MargaretA;Kemppainen,JenniferL;Horibe,Masayasu;Chandra,Shruti;Majumder,Shounak;Petersen,GloriaM;Rabe,KariG
• 通讯作者: Rabe,KariG

Accuracy of Smoking Status Reporting: Proxy Information in a Rapidly Fatal Cancer Setting.

• DOI: 10.1016/j.mayocpiqo.2020.07.010
• 发表时间: 2020-12
• 期刊: Mayo Clinic proceedings. Innovations, quality & outcomes
• 作者: Stevens MA;Rabe KG;Boursi B;Kolluri A;Singh DP;Bamlet WR;Petersen GM
• 通讯作者: Petersen GM

Influence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives.

• DOI: 10.1158/1055-9965.epi-21-0745
• 发表时间: 2022-03
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Antwi SO;Rabe KG;Bamlet WR;Meyer M;Chandra S;Fagan SE;Hu C;Couch FJ;McWilliams RR;Oberg AL;Petersen GM
• 通讯作者: Petersen GM

THSB2 as a prognostic biomarker for patients diagnosed with metastatic pancreatic ductal adenocarcinoma.

• DOI: 10.18632/oncotarget.28099
• 发表时间: 2021-10-26
• 期刊: Oncotarget
• 作者: Gimotty PA;Till JE;Udgata S;Takenaka N;Yee SS;LaRiviere MJ;O'Hara MH;Reiss KA;O'Dwyer P;Katona BW;Herman D;Carpenter EL;Zaret KS
• 通讯作者: Zaret KS