Program Official

Principal Investigator

Awardee Organization

University Of Tx Md Anderson Can Ctr
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Circulating Biomarkers and Imaging for Early Detection of Pancreatic Cancer

Biomarkers for the early detection of pancreatic cancer are urgently needed. However, individual molecules with the sensitivity and specificity needed for population-based screening have not been discovered. CA-19-9 has been studied extensively and yet has failed to demonstrate the predictive value necessary for early detection and diagnosis. Although many platforms, including proteomic, genomic and transcriptomic approaches have been utilized and biomarker candidates identified, no one platform or molecule has been successfully validated in large blinded population screens. We have taken a functional genomic pathways approach to biomarker discovery targeting the earliest genomic intervals altered in pancreatic and other smoking related cancers, focusing on biomarkers involved in critical cancer relevant cellular pathways. We have identified a “migration signature” and biomarker panel that has gone through two blinded validations including the NCI-EDRN pancreatic cancer reference set of early stage disease and benign and healthy controls. Results indicate that our panel of biomarkers improves the performance of CA19-9 to detect asymptomatic early stage pancreatic cancer yielding significant results across validations platforms. We have developed plasma miRNA biomarker panels for pancreatic cancer and validated these in multiple trials. The combination of our biomarkers demonstrates high sensitivity and specificity to detect early stage pancreatic cancer. We will further refine this early stage biomarker panel and a novel risk score approach to stratify the general population and at risk population for screening. Refined panels will be validated in large retrospective and prospective cohorts for early detection of pancreatic cancer according to ProBE design. In order that we identify early stage disease prior to metastasis, amenable to curative intervention, we will utilize a mousehuman approach to develop integrated biomarkers profiles from plasma and plasma exosomes to detect late precursor stage PanINs prior to development of advanced cancer with subsequent validation for a prediagnostic biomarker panel. We will also develop a novel two tiered screening strategy with validated biomarkers and novel imaging tools to change the clinical management plan and significantly improve survival of one of the most deadly cancers.


  • Dutta P, Perez MR, Lee J, Kang Y, Pratt M, Salzillo TC, Weygand J, Zacharias NM, Gammon ST, Koay EJ, Kim M, McAllister F, Sen S, Maitra A, Piwnica-Worms D, Fleming JB, Bhattacharya PK. Combining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer. Journal of proteome research. 2019 Jul 5;18(7):2826-2834. Epub 2019 Jun 4. PMID: 31120258
  • Hernandez S, Parra ER, Uraoka N, Tang X, Shen Y, Qiao W, Jiang M, Zhang S, Mino B, Lu W, Pandurengan R, Haymaker C, Affolter K, Scaife CL, Yip-Schneider M, Schmidt CM, Firpo MA, Mulvihill SJ, Koay EJ, Wang H, Wistuba II, Maitra A, Solis LM, Sen S. Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 May 2;28(9):1938-1947. PMID: 35491652
  • Rao Y, Gammon ST, Sutton MN, Zacharias NM, Bhattacharya P, Piwnica-Worms D. Excess exogenous pyruvate inhibits lactate dehydrogenase activity in live cells in an MCT1-dependent manner. The Journal of biological chemistry. 2021 Jul;297(1):100775. Epub 2021 May 20. PMID: 34022218
  • Cazoulat G, Gupta AC, Al Taie MM, Koay EJ, Brock KK. Analysis and prediction of liver volume change maps derived from computational tomography scans acquired pre- and post-radiation therapy. Physics in medicine and biology. 2023 Oct 4;68. (20). PMID: 37714187
  • Dittmar RL, Liu S, Tai MC, Rajapakshe K, Huang Y, Longton G, DeCapite C, Hurd MW, Paris PL, Kirkwood KS, Coarfa C, Maitra A, Brand RE, Killary AM, Sen S. Plasma miRNA Biomarkers in Limited Volume Samples for Detection of Early-stage Pancreatic Cancer. Cancer prevention research (Philadelphia, Pa.). 2021 Jul;14(7):729-740. Epub 2021 Apr 23. PMID: 33893071
  • Cazoulat G, Anderson BM, McCulloch MM, Rigaud B, Koay EJ, Brock KK. Detection of vessel bifurcations in CT scans for automatic objective assessment of deformable image registration accuracy. Medical physics. 2021 Oct;48(10):5935-5946. Epub 2021 Aug 25. PMID: 34390007
  • Park PC, Choi GW, M Zaid M, Elganainy D, Smani DA, Tomich J, Samaniego R, Ma J, Tamm EP, Beddar S, Koay EJ. Enhancement pattern mapping technique for improving contrast-to-noise ratios and detectability of hepatobiliary tumors on multiphase computed tomography. Medical physics. 2020 Jan;47(1):64-74. Epub 2019 Nov 19. PMID: 31449684
  • De B, Upadhyay R, Liao K, Kumala T, Shi C, Dodoo G, Abi Jaoude J, Corrigan KL, Manzar GS, Marqueen KE, Bernard V, Lee SS, Raghav KPS, Vauthey JN, Tzeng CD, Tran Cao HS, Lee G, Wo JY, Hong TS, Crane CH, Minsky BD, Smith GL, Holliday EB, Taniguchi CM, Koong AC, Das P, Javle M, Ludmir EB, Koay EJ. Definitive Liver Radiotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Metastases. Liver cancer. 2023 Mar 16;12(3):198-208. doi: 10.1159/000530134. eCollection 2023 Aug. PMID: 37593365
  • Pudakalakatti S, Raj P, Salzillo TC, Enriquez JS, Bourgeois D, Dutta P, Titus M, Shams S, Bhosale P, Kim M, McAllister F, Bhattacharya PK. Metabolic Imaging Using Hyperpolarization for Assessment of Premalignancy. Methods in molecular biology (Clifton, N.J.). 2022;2435:169-180. PMID: 34993946
  • Hu Q, Ye Y, Chan LC, Li Y, Liang K, Lin A, Egranov SD, Zhang Y, Xia W, Gong J, Pan Y, Chatterjee SS, Yao J, Evans KW, Nguyen TK, Park PK, Liu J, Coarfa C, Donepudi SR, Putluri V, Putluri N, Sreekumar A, Ambati CR, Hawke DH, Marks JR, Gunaratne PH, Caudle AS, Sahin AA, Hortobagyi GN, Meric-Bernstam F, Chen L, Yu D, Hung MC, Curran MA, Han L, Lin C, Yang L. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature immunology. 2019 Jul;20(7):835-851. Epub 2019 Jun 3. PMID: 31160797
  • De B, Tran Cao HS, Vauthey JN, Manzar GS, Corrigan KL, Raghav KPS, Lee SS, Tzeng CD, Minsky BD, Smith GL, Holliday EB, Taniguchi CM, Koong AC, Das P, Javle M, Ludmir EB, Koay EJ. Ablative liver radiotherapy for unresected intrahepatic cholangiocarcinoma: Patterns of care and survival in the United States. Cancer. 2022 Jul 1;128(13):2529-2539. Epub 2022 Apr 13. PMID: 35417569
  • Tovar DR, Rosenthal MH, Maitra A, Koay EJ. Potential of artificial intelligence in the risk stratification for and early detection of pancreatic cancer. Artificial intelligence surgery. 2023;3(1):14-26. Epub 2023 Mar 20. PMID: 37124705
  • McCowan CV, Salmon D, Hu J, Pudakalakatti S, Whiting N, Davis JS, Carson DD, Zacharias NM, Bhattacharya PK, Farach-Carson MC. Post-Acquisition Hyperpolarized 29Silicon Magnetic Resonance Image Processing for Visualization of Colorectal Lesions Using a User-Friendly Graphical Interface. Diagnostics (Basel, Switzerland). 2022 Mar 1;12. (3). PMID: 35328163
  • Song S, Tien CL, Cui H, Basil P, Zhu N, Gong Y, Li W, Li H, Fan Q, Min Choi J, Luo W, Xue Y, Cao R, Zhou W, Ortiz AR, Stork B, Mundra V, Putluri N, York B, Chu M, Chang J, Yun Jung S, Xie L, Song J, Zhang L, Sun Z. Myocardial Rev-erb-Mediated Diurnal Metabolic Rhythm and Obesity Paradox. Circulation. 2022 Feb 8;145(6):448-464. Epub 2022 Jan 17. PMID: 35034472
  • Koay EJ, Hanania AN, Hall WA, Taniguchi CM, Rebueno N, Myrehaug S, Aitken KL, Dawson LA, Crane CH, Herman JM, Erickson B. Dose-Escalated Radiation Therapy for Pancreatic Cancer: A Simultaneous Integrated Boost Approach. Practical radiation oncology. 2020 Nov-Dec;10(6):e495-e507. Epub 2020 Feb 13. PMID: 32061993
  • Semaan A, Bernard V, Wong J, Makino Y, Swartzlander DB, Rajapakshe KI, Lee JJ, Officer A, Schmidt CM, Wu HH, Scaife CL, Affolter KE, Nachmanson D, Firpo MA, Yip-Schneider M, Lowy AM, Harismendy O, Sen S, Maitra A, Jakubek YA, Guerrero PA. Integrated Molecular Characterization of Intraductal Papillary Mucinous Neoplasms: An NCI Cancer Moonshot Precancer Atlas Pilot Project. Cancer research communications. 2023 Oct 10;3(10):2062-2073. PMID: 37721516
  • Pudakalakatti S, Titus M, Enriquez JS, Ramachandran S, Zacharias NM, Shureiqi I, Liu Y, Yao JC, Zuo X, Bhattacharya PK. Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors. International journal of molecular sciences. 2022 Jan 31;23. (3). PMID: 35163565
  • Ambati CR, Vantaku V, Donepudi SR, Amara CS, Ravi SS, Mandalapu A, Perla M, Putluri V, Sreekumar A, Putluri N. Measurement of methylated metabolites using Liquid Chromatography-Mass Spectrometry and its biological application. Analytical methods : advancing methods and applications. 2019 Jan 7;11(1):49-57. Epub 2018 Nov 15. PMID: 31762797
  • Sharma G, Enriquez JS, Armijo R, Wang M, Bhattacharya P, Pudakalakatti S. Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1-13C Pyruvate MRSI. Metabolites. 2023 Apr 28;13. (5). PMID: 37233647
  • Odunsi K, Qian F, Lugade AA, Yu H, Geller MA, Fling SP, Kaiser JC, Lacroix AM, D'Amico L, Ramchurren N, Morishima C, Disis ML, Dennis L, Danaher P, Warren S, Nguyen VA, Ravi S, Tsuji T, Rosario S, Zha W, Hutson A, Liu S, Lele S, Zsiros E, McGray AJR, Chiello J, Koya R, Chodon T, Morrison CD, Putluri V, Putluri N, Mager DE, Gunawan R, Cheever MA, Battaglia S, Matsuzaki J. Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses. Science translational medicine. 2022 Mar 16;14(636):eabg8402. Epub 2022 Mar 16. PMID: 35294258
  • Gastelum G, Jiang W, Wang L, Zhou G, Borkar R, Putluri N, Moorthy B. Polycyclic Aromatic Hydrocarbon-induced Pulmonary Carcinogenesis in Cytochrome P450 (CYP)1A1- and 1A2-Null Mice: Roles of CYP1A1 and CYP1A2. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Oct 1;177(2):347-361. PMID: 32726451
  • Douglas JE, Liu S, Ma J, Wolff RA, Pant S, Maitra A, Tamm EP, Bhosale P, Katz MHG, Varadhachary GR, Koay EJ. PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer. BMC cancer. 2022 Jan 3;22(1):14. PMID: 34980020
  • Syed M, Cagely M, Dogra P, Hollmer L, Butner JD, Cristini V, Koay EJ. Immune-checkpoint inhibitor therapy response evaluation using oncophysics-based mathematical models. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology. 2023 Mar;15(2):e1855. Epub 2022 Sep 23. PMID: 36148978
  • Purushothaman A, Oliva-Ramírez J, Treekitkarnmongkol W, Sankaran D, Hurd MW, Putluri N, Maitra A, Haymaker C, Sen S. Differential Effects of Pancreatic Cancer-Derived Extracellular Vesicles Driving a Suppressive Environment. International journal of molecular sciences. 2023 Sep 27;24. (19). PMID: 37834100
  • Wang CX, Elganainy D, Zaid MM, Butner JD, Agrawal A, Nizzero S, Minsky BD, Holliday EB, Taniguchi CM, Smith GL, Koong AC, Herman JM, Das P, Maitra A, Wang H, Wolff RA, Katz MHG, Crane CH, Cristini V, Koay EJ. Mass Transport Model of Radiation Response: Calibration and Application to Chemoradiation for Pancreatic Cancer. International journal of radiation oncology, biology, physics. 2022 Sep 1;114(1):163-172. Epub 2022 May 26. PMID: 35643254
  • Koay EJ, Zaid M, Aliru M, Bagereka P, Van Wieren A, Rodriguez MJ, Jacobson G, Wolff RA, Overman M, Varadhachary G, Pant S, Wang H, Tzeng CW, Ikoma N, Kim M, Lee JE, Katz MH, Tamm E, Bhosale P, Taniguchi CM, Holliday EB, Smith GL, Ludmir EB, Minsky BD, Crane CH, Koong AC, Das P, Wang X, Javle M, Krishnan S. Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation. International journal of radiation oncology, biology, physics. 2022 Nov 1;114(3):444-453. Epub 2022 Jul 18. PMID: 35863672
  • Enriquez JS, Chu Y, Pudakalakatti S, Hsieh KL, Salmon D, Dutta P, Millward NZ, Lurie E, Millward S, McAllister F, Maitra A, Sen S, Killary A, Zhang J, Jiang X, Bhattacharya PK, Shams S. Hyperpolarized Magnetic Resonance and Artificial Intelligence: Frontiers of Imaging in Pancreatic Cancer. JMIR medical informatics. 2021 Jun 17;9(6):e26601. PMID: 34137725