Pancreatic Ductal Adenocarcinoma (PDAC)
is the most common type of pancreatic cancer and the 7th highest cause of mortality related to cancer , . In spite of the progress in the field, the diagnosis and hence, the treatment of PDAC remains challenging, due to the late presentation of the disease .
The early detection of the disease
is hindered by the lack of symptoms at these stages, as well as the ineffectiveness of the available diagnostic methods. The diagnosis of PDAC depends mostly on imaging techniques that are incapable of detecting the early-lesions and usually, the possible benefit for the patient does not outweigh the harm , , .
This year, we present Metis
a cost-effective, non-invasive tool for the early diagnosis of PDAC. Metis, utilizes an upcoming kind of biomarkers, miRNAs, that are dysregulated during stage I and II of PDAC and secreted in urine. We intend to design a tool that carries out the diagnosis of PDAC, through the quantification of these molecules in urine samples , .
Our system consists
of a new type of engineered riboswitches, Toehold Switches, RNA molecules, that contain a hairpin-like structure which allows the controlled production of a fluorescent protein, eGFP, which functions as a reporter gene. The hairpin structure of Toeholds inhibits the binding of ribosomes and consequently, the expression of the reporter gene , .
- | World Health Organization, “Pancreatic cancer fact sheet,” Cancer Today, 2020. https://gco.iarc.fr/today/fact-sheets-cancers (accessed May 04, 2021).
| A. McGuigan, P. Kelly, R. C. Turkington, C. Jones, H. G. Coleman, and R. S. McCain, “Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes,” World Journal of Gastroenterology, vol. 24, no. 43. pp. 4846–4861, Nov. 2018.
| R. Słotwiński, G. Lech, and S. M. Słotwińska. “MicroRNAs in pancreatic cancer diagnosis and therapy,” Central European Journal of Immunology, vol. 43, no. 3, pp. 314–324, Oct. 2018.
| P. F. Laeseke, R. Chen, R. B. Jeffrey, T. A. Brentnall, and J. K. Willmann, “Combining in vitro diagnostics with in vivo imaging for earlier detection of pancreatic ductal adenocarcinoma: Challenges and solutions,” Radiology, vol. 277, no. 3, pp. 644–661, Dec. 2015.
| J. D. Schiffman, P. G. Fisher, and P. Gibbs, “Early Detection of Cancer : Past , Present , and Future”, American Society of Clinical Oncology Educational Book, vol. 35, pp. 57–65, 2015.
| M. V. Iorio, and C. M. Croce, “MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review,” EMBO Molecular Medicine, vol. 4, no. 3, pp. 143–159, Mar. 2012.
| A. Z. Daoud, E. J. Mulholland, G. Cole, and H. O. McCarthy, “MicroRNAs in Pancreatic Cancer: Biomarkers, prognostic, and therapeutic modulators,” BMC Cancer, vol. 19, no. 1, pp. 1–13, Nov. 2019.
| A. Green, P. A. Silver, J. J. Collins, and P. Yin, “Toehold switches: De-novo-designed regulators of gene expression,” Cell, vol. 159, no. 4, pp. 925–939, Nov. 2014.
| K. Pardee, A. Green, M. K. Takahashi, D. Braff, G. Lambert, J. Woo Lee, T. Ferrante, D. Ma, N. Donghia, M. Fan, N. M. Daringer, I. Bosch, D. M. Dudley, D. H. O'Connor, L. Gehrke, J. J. Collins, “Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components,” Cell, vol. 165, no. 5, pp. 1255–1266, May 2016.