Principal Investigator
Brian B.
Haab
Awardee Organization
Van Andel Research Institute
United States
Fiscal Year
2021
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 3U01CA152653-10S1
Detection and prognosis of early-stage pancreatic cancer by interdependent plasma markers
Pancreatic cancer is alone among the major cancers in its increasing prevalence, and it is predicted to be the second-leading cause of cancer death by 2030. A strategy to help reverse this trend is to identify and treat more pancreatic cancers at an early stage of the disease, when surgery and therapeutics are most effective. Currently no biomarker is good enough to be used for the detection of early-stage disease in people at elevated risk for pancreatic cancer. In our preliminary research, we have developed biomarkers a) that have better sensitivity and specificity for early-stage cancer than the current best biomarker for pancreatic cancer, CA 19-9, and b) that can detect cancers that are low in CA 19-9. The several individual biomarkers complement each other because each is elevated in distinct groups of patients. These encouraging results lead us to propose that a biomarker panel developed from these and related biomarkers will provide the necessary performance to enable clinical detection and diagnosis of early-stage pancreatic cancer. A second strategy for improving outcomes is to better identify those early-stage cancers that will rapidly progress. Some cancers that appear to be early-stage and resectable show progression within a short time after surgery. Biomarkers to identify such cancers would allow better treatment for those patients, as they could be spared the risk and recovery time of surgery and immediately begin the appropriate systemic treatment, likely leading to better results. Currently, we have no accurate indicators of rapid progression after surgery. One of the biomarkers discovered in our preliminary research is elevated in most patients who have rapid progression after surgery, suggesting the possibility of its use as a progression biomarker. Our goal is to develop biomarkers that will be effective for detecting early-stage pancreatic cancer (Aim 1) and for identifying the early-stage cancers that will rapidly progress (Aim 2). We will pursue this goal by optimizing the existing biomarkers and bolstering them with additional biomarkers, and by developing, testing, and validating panels of biomarkers that improve performance over the individual biomarkers. We hypothesize that the biomarker panels can achieve the performance required for further clinical validation. We are in a good position to achieve our goal, given the promising biomarkers already discovered and the convergence of all the other factors necessary for a successful project: we have assembled a team of top experts in the clinical, technological, and statistical fields, plus we have the sample resources, patient base, experimental methods, institutional environment and support, and passion as a team to deliver high-impact results.
- Liu Y, Kaur S, Huang Y, Fahrmann JF, Rinaudo JA, Hanash SM, Batra SK, Singhi AD, Brand RE, Maitra A, Haab BB. Biomarkers and Strategy to Detect Preinvasive and Early Pancreatic Cancer: State of the Field and the Impact of the EDRN. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Dec;29(12):2513-2523. Epub 2020 Jun 12. PMID: 32532830
- Staal B, Liu Y, Barnett D, Hsueh P, He Z, Gao C, Partyka K, Hurd MW, Singhi AD, Drake RR, Huang Y, Maitra A, Brand RE, Haab BB. The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 May 1;25(9):2745-2754. Epub 2019 Jan 7. PMID: 30617132
- Yue T, Maupin KA, Fallon B, Li L, Partyka K, Anderson MA, Brenner DE, Kaul K, Zeh H, Moser AJ, Simeone DM, Feng Z, Brand RE, Haab BB. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers. PloS one. 2011;6(12):e29180. Epub 2011 Dec 29. PMID: 22220206
- Haab B, Qian L, Staal B, Jain M, Fahrmann J, Worthington C, Prosser D, Velokokhatnaya L, Lopez C, Tang R, Hurd MW, Natarajan G, Kumar S, Smith L, Hanash S, Batra SK, Maitra A, Lokshin A, Huang Y, Brand RE. A rigorous multi-laboratory study of known PDAC biomarkers identifies increased sensitivity and specificity over CA19-9 alone. Cancer letters. 2024 Nov 1;604:217245. Epub 2024 Sep 12. PMID: 39276915
- Binkowski B, Klamer Z, Gao C, Staal B, Repesh A, Tran HL, Brass DM, Bartlett P, Gallinger S, Blomqvist M, Morrow JB, Allen P, Shi C, Singhi A, Brand R, Huang Y, Hostetter G, Haab BB. Multiplexed glycan immunofluorescence identification of pancreatic cancer cell subpopulations in both tumor and blood samples. Science advances. 2025 Mar 7;11(10):eadt0029. Epub 2025 Mar 7. PMID: 40053601
- Chopra A, Zamora R, Vodovotz Y, Hodges JC, Barclay D, Brand R, Simmons RL, Lee KK, Paniccia A, Murthy P, Lotze MT, Boone BA, Zureikat AH. Baseline Plasma Inflammatory Profile Is Associated With Response to Neoadjuvant Chemotherapy in Patients With Pancreatic Adenocarcinoma. Journal of immunotherapy (Hagerstown, Md. : 1997). 2021 Jun 1;44(5):185-192. PMID: 33935273
- Binkowski B, Klamer Z, Gao C, Staal B, Repesh A, Tran HL, Brass DM, Bartlett P, Gallinger S, Blomqvist M, Morrow JB, Allen P, Shi C, Singhi A, Brand R, Huang Y, Hostetter G, Haab BB. Multiplexed Glycan Immunofluorescence Identification of Pancreatic Cancer Cell Subpopulations in Both Tumor and Blood Samples. bioRxiv : the preprint server for biology. 2024 Aug 23. PMID: 39229066
- Sinha J, Cao Z, Dai J, Tang H, Partyka K, Hostetter G, Simeone DM, Feng Z, Allen PJ, Brand RE, Haab BB. A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas. PloS one. 2016 Dec 19;11(12):e0167070. doi: 10.1371/journal.pone.0167070. eCollection 2016. PMID: 27992432
- Chao DT, Shah NH, Zeh HJ 3rd, Singhi AD, Bahary N, McGrath KM, Fasanella KE, Zureikat AH, Whitcomb DC, Brand RE. Overweight or Obese Individuals at Eighteen Years of Age Develop Pancreatic Adenocarcinoma at a Significantly Earlier Age. Gastroenterology research and practice. 2018 Jun 5;2018:2380596. doi: 10.1155/2018/2380596. eCollection 2018. PMID: 29967636