Current State of Animal (Mouse) Modeling in Melanoma Research.
Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Omer F
OF
Kuzu
The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Felix D
FD
Nguyen
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Mohammad A
MA
Noory
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Arati
A
Sharma
genetically engineered mouse models (GEMMs); melanoma; patient-derived tumor xenografts (PDTXs); syngeneic models; xenografts