TY - JOUR
T1 - Animal models of gastrointestinal and liver diseases. the difficulty of animal modeling of pancreatic cancer for preclinical evaluation of therapeutics
AU - Logsdon, Craig D.
AU - Arumugam, Thiruvengadam
AU - Ramachandran, Vijaya
N1 - Publisher Copyright:
© 2015 the American Physiological Society.
PY - 2015/9/4
Y1 - 2015/9/4
N2 - Pancreatic ductal adenocarcinoma (PDAC) is relatively rare but extremely lethal. Standard cytotoxic therapeutics provide little benefit. To date, newer targeted therapeutics have also not been highly successful. Often novel therapeutics that have appeared to perform well in preclinical models have failed in the clinic. Many factors contribute to these failures, but the one most often attributed is the shortcomings of the preclinical models. A plethora of animal models now exist for PDAC, including cell line xenografts, patient-derived xenografts, a wide variety of genetic mouse models, and syngeneic xenografts. These models have generated a tremendous amount of information useful for the understanding of PDAC. Yet none seems to well predict clinical outcomes of new treatments. This review will discuss how genetic instability and cellular heterogeneity make this disease so difficult to model accurately. We will also discuss the strengths and weaknesses of many of the popular models. Ultimately we will argue that there is no perfect model and that the best approach to understanding clinical performance is the use of multiple preclinical models with an understanding of their salient features.
AB - Pancreatic ductal adenocarcinoma (PDAC) is relatively rare but extremely lethal. Standard cytotoxic therapeutics provide little benefit. To date, newer targeted therapeutics have also not been highly successful. Often novel therapeutics that have appeared to perform well in preclinical models have failed in the clinic. Many factors contribute to these failures, but the one most often attributed is the shortcomings of the preclinical models. A plethora of animal models now exist for PDAC, including cell line xenografts, patient-derived xenografts, a wide variety of genetic mouse models, and syngeneic xenografts. These models have generated a tremendous amount of information useful for the understanding of PDAC. Yet none seems to well predict clinical outcomes of new treatments. This review will discuss how genetic instability and cellular heterogeneity make this disease so difficult to model accurately. We will also discuss the strengths and weaknesses of many of the popular models. Ultimately we will argue that there is no perfect model and that the best approach to understanding clinical performance is the use of multiple preclinical models with an understanding of their salient features.
KW - Genetic mouse models
KW - Pancreatic ductal adenocarcinoma
KW - Xenografts
UR - http://www.scopus.com/inward/record.url?scp=84940731994&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940731994&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00169.2015
DO - 10.1152/ajpgi.00169.2015
M3 - Article
C2 - 26159697
AN - SCOPUS:84940731994
SN - 0193-1857
VL - 309
SP - G283-G291
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 5
ER -