Upcoming Revolutionary Paths in Preclinical Modeling of Pancreatic Adenocarcinoma

To date, PDAC remains the cancer having the worst prognosis with mortality rates constantly on the rise. Efficient cures are still absent, despite all attempts to understand the aggressive physiopathology underlying this disease. A major stumbling block is the outdated preclinical modeling strategies applied in assessing effectiveness of novel anticancer therapeutics. Current in vitro preclinical models have a low fidelity to mimic the exact architectural and functional complexity of PDAC tumor found in human set, due to the lack of major components such as immune system and tumor microenvironment with its associated chemical and mechanical signals. The existing PDAC preclinical platforms are still far from being reliable and trustworthy to guarantee the success of a drug in clinical trials. Therefore, there is an urgent demand to innovate novel in vitro preclinical models that mirrors with precision tumor-microenvironment interface, pressure of immune system, and molecular and morphological aspects of the PDAC normally experienced within the living organ. This review outlines the traditional preclinical models of PDAC namely 2D cell lines, genetically engineered mice, and xenografts, and describing the present famous approach of 3D organoids. We offer a detailed narration of the pros and cons of each model system. Finally, we suggest the incorporation of two off-center newly born techniques named 3D bio-printing and organs-on-chip and discuss the potentials of swine models and in silico tools, as powerful new tools able to transform PDAC preclinical modeling to a whole new level and open new gates in personalized medicine.