Preclinical models of pancreatic ductal adenocarcinoma: challenges and opportunities in the era of precision medicine

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal malignancy, with an average 5-year survival rate of 9% (Siegel RL, Miller KD, Jemal A. Ca Cancer J Clin. 2019;69(1):7-34). The steady increase in mortality rate indicates limited efficacy of the conventional regimen. The heterogeneity of PDAC calls for personalized treatment in clinical practice, which requires the construction of a preclinical system for generating patient-derived models. Currently, the lack of high-quality preclinical models results in ineffective translation of novel targeted therapeutics. This review summarizes applications of commonly used models, discusses major difficulties in PDAC model construction and provides recommendations for integrating workflows for precision medicine.

Challenges in genomic analysis of model systems and primary tumors of pancreatic ductal adenocarcinoma

“…Clonal evolution occurs during passaging and constructing model systems as well as tumor progression and metastasis in the patient [51] . PDX was not accurately reflected in the heterogeneity of metastatic tumors due to clonal evolution analysis from primary tumors [45] .…”

DNA Damage Repair Deficiency in Pancreatic Ductal Adenocarcinoma: Preclinical Models and Clinical Perspectives

“…Target discovery and successful development of targeted therapies is highly dependent on the relevance of the preclinical models used and therapies frequently fail at the transition to clinical trials. Multiple recent papers are available which review the preclinical models used in PDAC research ( Moreira et al, 2018 ; Garcia et al, 2020 ; Swayden et al, 2020 ; Yu et al, 2021 ). This review will extend upon published literature by focusing on the application of these models to further target DDR pathways.…”

Carcinoembryonic antigen as a specific glycoprotein ligand of rBC2LCN lectin on pancreatic ductal adenocarcinoma cells

“…Despite numerous attempts to disclose the weaknesses of pancreatic ductal adenocarcinoma (PDAC), useful and definitive targets have not been elucidated to date 1 . In the fight against PDAC, we have focused on cell surface glycans because all cells are covered with a glycan layer referred to as the glycocalyx 2 .…”