Explorations in the development of novel early diagnosis and disease monitoring tools in digestive tract cancers

Abstract

Exploring the possibility that genomic DNA (exoDNA) may represent a highly promising next-generation biomarker for early detection. The research team hope to validate the use of circulating exoDNA as a new generation biomarker using KRAS mutation status as a surrogate source of primary tumour information. This may be useful for early diagnosis in cases of pancreatic biliary cancer (PBC) and a valid tool for clinical decision making, disease monitoring and therapeutic stratification. Point mutations in KRAS are found in 50% of gallbladder cancers, thus the team will use an ultra-sensitive droplet digital PCR (ddPCR) platform to identify mutant KRAS in samples of circulating exoDNA isolated from 75 early stage pancreatic biliary cancer patients at the time of diagnosis. These samples will be matched with exoDNA from 'benign disease' controls that have been match on the basis of age and gender. Roa hopes to use exoDNA to query the 'actionable' exome in PBC using a head-to-head comparison using next generation sequencing. Bizama's main objective in investigating patient-derived organoids is to establish and characterise organoid cultures from GBC patients in order to evaluate the drug responses of these organoids both to standard treatments and to specific pathway inhibitors. Current human GBC research lacks in vitro models that can capture the pathophysiological traits of the original tumour and normal epithelia. The research team hope to demonstrate that organoid cultures can be successfully established from normal and tumour gallbladder tissues from Chilean patients and that these organoids will be representative of the primary specimens. The team plan to develop an organoid culture platform as a prototype for the prediction of prognosis and efficiency of standard and targeted therapy. This ex vivo organoids model project may help clinicians predict the response of particular patients to specific treatments, thus avoiding unnecessary therapies.