Animal models for modeling pancreatic cancer and novel drug discovery

ABSTRACT

Introduction: Despite the introduction of novel therapeutic regimens for advanced stages of pancreatic cancer, long-term survival and overall outcome for patients are still very poor. Suitable small animal models are a prerequisite for better understanding of underlying pathophysiology and for translational studies designed to uncover novel therapeutic targets and to evaluate therapy regimens on a preclinical level.

Areas covered: Genetically engineered mouse models as well as syngenic and xenotransplantation models are summarized and critically discussed with respect to their value for pancreatic cancer translational research.

Expert opinion: Mouse models of pancreatic cancer represent a valuable tool for translational studies and are indispensable in order to develop novel potent drugs against pancreatic cancer. More complex genetically engineered mouse models are being developed to cover the complex genomic alterations found in human pancreatic cancers and to enable studies correlating genotype with response to specific therapeutic interventions. Another promising area of research in this field is the refinement and further development of humanized patient-derived xenograft models.

KEYWORDS:

• Pancreatic cancer
• translational research
• patient-derived xenografts
• genetically engineered mouse models

Article highlights

• Pancreatic cancer remains a dire malignancy with an extremely poor overall prognosis; the introduction of novel combinatorial chemotherapeutic regimens has so far not led to a relevant improvement in long-term survival.

• Small animal models are indispensable to enable translational studies in this field.

• Available genetically engineered mouse models (GEMM) of pancreatic cancer faithfully recapitulate most key phenotypic features of human pancreatic cancer.

• Advanced GEMMs are developed to model specific genetic conditions and to better understand the clinical relevance of low-frequency driver mutations.

• Humanized patient-derived xenograft models are being developed to enable translational studies of immuno-oncological therapeutic concepts.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

European Union’s Horizon 2020 research and innovation program via Marie Skłodowska-Curie grant agreement No 671881. They are also supported by the Medical Faculty of the University of Bonn (BONFOR) via grant O-142.0018.