Advances in Liquid Biopsy for Early Detection and Monitoring of Pancreatic Cancer

Authors

  • Ubaid Ur Rehman North Surgical Ward, Mayo Hospital Lahore/King Edward Medical University, Lahore, Punjab, Pakistan.
  • Fiza Rehman Lahore Medical and Dental College/Ghurkhi Hospital Lahore, Punjab, Pakistan.
  • Quratulain Badar Department of Oncology, Ziauddin University and Hospital Karachi, Sindh, Pakistan.
  • Falaq Shahid Opthalmology Unit 2, Mayo Hospital Lahore/King Edward Medical University, Lahore, Punjab, Pakistan.
  • Adil Mohammad State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China.
  • Syed Rizvan Ali Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Punjab, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i1.575

Keywords:

Liquid Biopsy, Pancreatic Cancer, Circulating Tumor DNA (ctDNA), Circulating Tumor Cells (CTCs),, Exosomes, Early Detection, Real-time Monitoring, Personalized Medicine,, Next-generation Sequencing (NGS), Biomarker Discovery

Abstract

Pancreatic cancer is a rather aggressive form of malignancy. It characteristically presents at an advanced stage and progresses aggressively. The liquid biopsy has revolutionized the diagnosis and monitoring approach. The present review provides details on current progress, clinical utility, and the challenge in applying the method for managing pancreatic cancer. These can shed light on tumor biology, molecular changes, and treatment responses with the examination of tumor-derived fluids like ctDNA, CTCs, and exosomes. Among the technologies which could enhance sensitivity and specificity to make this a more viable test for early detection and real-time monitoring are next-generation sequencing and microfluidics and other highly advanced exosome isolation techniques. Such clinical studies have only revealed recent times that liquid biopsy is indeed useful in the detection of hallmark mutations, such as KRAS and TP53, prognosis assessment, and therapeutic efficacy monitoring. Recent trends in multi-omics integration and artificial intelligence-driven biomarker discovery as well as liquid biopsy-based developing point-of-care diagnostic devices highlight the potential of revolutionizing personalized medicine. Despite its promise, some challenges that include low abundance of biomarkers, lack of standardization, and high costs characterize what limits acceptance of liquid biopsy in clinical practice. This review outlines the role which liquid biopsy can play in conquest of the challenges of diagnosis and therapy of pancreatic cancer. Concomitantly, it discusses future requirements for research, technological breakthroughs, and a collaborative attitude toward overcoming prevalent limitations. Multidisciplinary approaches in the fields of multi-omics, artificial intelligence, and scalable diagnostic tools hold the promise of enhanced early detection of pancreatic cancer and optimization of treatment strategies in the patients themselves.

Downloads

Download data is not yet available.

References

Alix-Panabières, C., & Pantel, K. (2021). Liquid biopsy: from discovery to clinical application. Cancer discovery, 11(4), 858-873. https://doi.org/10.1158/2159-8290.CD-20-1311

Bardelli, A., & Pantel, K. (2017). Liquid Biopsies, What We Do Not Know (Yet). Cancer Cell, 31(2), 172-179. https://doi.org/10.1016/j.ccell.2017.01.002

Bettegowda, C., Sausen, M., Leary, R. J., Kinde, I., Wang, Y., Agrawal, N., ... & Diaz Jr, L. A. (2014). Detection of circulating tumor DNA in early-and late-stage human malignancies. Science translational medicine, 6(224), 224ra24-224ra24. https://doi.org/10.1126/scitranslmed.3007094

Bidard, F. C., Peeters, D. J., Fehm, T., Nolé, F., Gisbert-Criado, R., Mavroudis, D., ... & Pierga, J. Y. (2018). Clinical application of circulating tumor cells in breast cancer: Overview of the current interventional trials. Cancer Metastasis Reviews, 37(4), 749-772. https://doi.org/10.1007/s10555-018-9774-4

Canto, M. I., Harinck, F., Hruban, R. H., Offerhaus, G. J., Poley, J.-W., Kamel, I., Nio, Y., Schulick, R. S., Bassi, C., Kluijt, I., Levy, M. J., Chak, A., Fockens, P., Goggins, M., & Bruno, M. (2013). International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 62(3), 339–347. https://doi.org/10.1136/gutjnl-2012-303108

Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., & Chan, T. A. (2018). Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science (New York, N.Y.), 359(6375), 582–587. https://doi.org/10.1126/science.aao4572

Clancy, E. (2023). ACS Report Shows Prostate Cancer on the Rise, Cervical Cancer on the Decline. Renal & Urology News, NA-NA.

Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., ... & Vogelstein, B. (2017). Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science, 359(6378), 926-930. https://doi.org/10.1126/science.aar3247

Golan, T., Hammel, P., Reni, M., Van Cutsem, E., Macarulla, T., Hall, M. J., Park, J.-O., Hochhauser, D., Arnold, D., Oh, D.-Y., Reinacher-Schick, A., Tortora, G., Algül, H., O’Reilly, E. M., McGuinness, D., Cui, K. Y., Schlienger, K., Locker, G. Y., & Kindler, H. L. (2019). Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. New England Journal of Medicine, 381(4), 317–327. https://doi.org/10.1056/nejmoa1903387

Groot, V. P., Rezaee, N., Wu, W., Cameron, J. L., Fishman, E. K., Hruban, R. H., & Weiss, M. J. (2021). Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Annals of Surgery, 273(3), 759-765. https://doi.org/10.1097/SLA.0000000000003284

Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N., & DePinho, R. A. (2006). Genetics and biology of pancreatic ductal adenocarcinoma. Genes & development, 20(10), 1218-1249.

Hidalgo, M. (2010). Pancreatic cancer. New England Journal of Medicine, 362(17), 1605-1617. https://doi.org/10.1056/NEJMra0901557

Howlader, N., Chen, H., Noone, A., Miller, D., Byrne, J., Negoita, S., Cronin, K. A., & Mariotto, A. B. (2024). Impact of COVID-19 on 2021 cancer incidence rates and potential rebound from 2020 decline. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djae180

Hrstka, R., Bouchalova, P., Michalova, E., Matoulkova, E., Muller, P., Coates, P. J., & Vojtesek, B. (2015). AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10‐mediated regulatory pathway. Molecular Oncology, 10(5), 652-662. https://doi.org/10.1016/j.molonc.2015.12.003

Humphris, J., Chang, D., Johns, A., Scarlett, C., Pajic, M., Jones, M., Colvin, E., Nagrial, A., Chin, V., Chantrill, L., Samra, J., Gill, A., Kench, J., Merrett, N., Das, A., Musgrove, E., Sutherland, R., & Biankin, A. (2012). The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Annals of Oncology, 23(7), 1713-1722. https://doi.org/10.1093/annonc/mdr561

Kahlert, C., Melo, S. A., Protopopov, A., Tang, J., Seth, S., Koch, M., Zhang, J., Weitz, J., Chin, L., Futreal, A., & Kalluri, R. (2014). Identification of double-stranded Genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum Exosomes of patients with pancreatic cancer. Journal of Biological Chemistry, 289(7), 3869-3875. https://doi.org/10.1074/jbc.c113.532267

Kamisawa, T., Wood, L. D., Itoi, T., & Takaori, K. (2016). Pancreatic cancer. The Lancet, 388(10039), 73-85. https://doi.org/10.1016/s0140-6736(16)00141-0

Kanda, M., Matthaei, H., Wu, J., Hong, S. M., Yu, J., Borges, M., ... & Hruban, R. H. (2012). Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Clinical Cancer Research, 18(22), 5487-5496. https://doi.org/10.1158/1078-0432.CCR-12-1215

Makohon-Moore, A., & Iacobuzio-Donahue, C. A. (2016). Pancreatic cancer biology and genetics from an evolutionary perspective. Nature Reviews Cancer, 16(9), 553-565. https://doi.org/10.1038/nrc.2016.66

Mayers, J. R., Wu, C., Clish, C. B., Kraft, P., Torrence, M. E., Fiske, B. P., ... & Vander Heiden, M. G. (2014). Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nature Medicine, 20(10), 1193-1198. https://doi.org/10.1038/nm.3686

Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., & Kalluri, R. (2015). Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature, 523(7559), 177-182. https://doi.org/10.1038/nature14581

Mouliere, F., Chandrananda, D., Piskorz, A. M., Moore, E. K., Morris, J., Ahlborn, L. B., ... & Rosenfeld, N. (2018). Enhanced detection of circulating tumor DNA by fragment size analysis. Science Translational Medicine, 10(466), eaat4921. https://doi.org/10.1126/scitranslmed.aat4921

Rah, B., Banday, M. A., Bhat, G. R., Shah, O. J., Jeelani, H., Kawoosa, F., Yousuf, T., & Afroze, D. (2021). Evaluation of biomarkers, genetic mutations, and epigenetic modifications in early diagnosis of pancreatic cancer. World Journal of Gastroenterology, 27(36), 6093-6109. https://doi.org/10.3748/wjg.v27.i36.6093

Ryan, D. P., Hong, T. S., & Bardeesy, N. (2014). Pancreatic adenocarcinoma. New England Journal of Medicine, 371(11), 1039-1049. https://doi.org/10.1056/NEJMra1404198

Siravegna, G., Marsoni, S., Siena, S., & Bardelli, A. (2017). Integrating liquid biopsies into the management of cancer. Nature Reviews Clinical Oncology, 14(9), 531-548. https://doi.org/10.1038/nrclinonc.2017.14

Vincent, A., Herman, J., Schulick, R., Hruban, R. H., & Goggins, M. (2011). Pancreatic cancer. The Lancet, 378(9791), 607-620. https://doi.org/10.1016/s0140-6736(10)62307-0

Visser, C. W., Kamperman, T., Karbaat, L. P., Lohse, D., & Karperien, M. (2018). In-air microfluidics enables rapid fabrication of emulsions, suspensions, and 3D modular (bio)materials. Science Advances, 4(1). https://doi.org/10.1126/sciadv.aao1175

Waddell, N., Pajic, M., Patch, A. M., Chang, D. K., Kassahn, K. S., Bailey, P., ... & Grimmond, S. M. (2015). Whole genomes redefine the mutational landscape of pancreatic cancer. Nature, 518(7540), 495-501. https://doi.org/10.1038/nature14169

Wan, J. C., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017). Liquid biopsies come of age: Towards implementation of circulating tumour DNA. Nature Reviews Cancer, 17(4), 223-238. https://doi.org/10.1038/nrc.2017.7

Wang, P., Wang, Y., Hang, B., Zou, X., & Mao, J. H. (2015). A novel gene expression-based prognostic scoring system to predict survival in gastric cancer. Oncotarget, 7(34), 55343-55351. https://doi.org/10.18632/oncotarget.10725

Zhou, B., Xu, J. W., Cheng, Y. G., Gao, J. Y., Hu, S. Y., Wang, L., ... & Wang, W. (2018). Early detection of pancreatic cancer: Where are we now and where are we going? International Journal of Cancer, 141(2), 231-241. https://doi.org/10.1002/ijc.30892

Zill, O. A., Greene, C., Sebisanovic, D., Siew, L. M., Leng, J., Vu, M., ... & Collisson, E. A. (2015). Cell-free DNA next-generation sequencing in pancreatobiliary carcinomas. Cancer Discovery, 5(10), 1040-1048. https://doi.org/10.1158/2159-8290.CD-15-0274

Downloads

Published

2025-01-29

How to Cite

Rehman, U. U., Rehman , F., Quratulain Badar, Falaq Shahid, Adil Mohammad, & Syed Rizvan Ali. (2025). Advances in Liquid Biopsy for Early Detection and Monitoring of Pancreatic Cancer. Indus Journal of Bioscience Research, 3(1), 662-674. https://doi.org/10.70749/ijbr.v3i1.575