Genetic Dissection of Cancer Development, Therapy Response, and Resistance in Mouse Models of Breast Cancer.
The cancer genomics revolution has rapidly expanded the inventory of somatic mutations characterizing human malignancies, highlighting a previously underappreciated extent of molecular variability between and within patients. Also in breast cancer, the most commonly diagnosed malignancy in women, this heterogeneity complicates the understanding of the stepwise sequence of pathogenic events and the design of effective and long-lasting target therapies. To disentangle this complexity and pinpoint which molecular perturbations are crucial to hijack the cellular machinery and lead to tumorigenesis and drug resistance, functional studies are needed in model systems that faithfully and comprehensively recapitulate all the salient aspects of their cognate human counterparts. Mouse models of breast cancer have been instrumental for the study of tumor initiation and drug response but also involve cost and time limitations that represent serious bottlenecks in translational research. To keep pace with the overwhelming amount of hypotheses that warrant in vivo testing, continuous refinement of current breast cancer models and implementation of new technologies is crucial. In this review, we summarize the current state of the art in modeling human breast cancer in mice, and we put forward our vision for future developments.
Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Stefano
S
Annunziato
Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Marco
M
Barazas
Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.|Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Sven
S
Rottenberg
Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.|Cancer Genomics Netherlands, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Jos
J
Jonkers
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D051379:Mice