Rational Design of Mouse Models for Cancer Research.

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models.

[1]  S. Bhatia,et al.  Towards a Humanized Mouse Model of Liver Stage Malaria Using Ectopic Artificial Livers , 2017, Scientific Reports.

[2]  Ali Najafi,et al.  Seminars in Cancer Biology , 2014 .

[3]  Wen Jiang,et al.  Breaking Down the Barriers to Precision Cancer Nanomedicine. , 2017, Trends in biotechnology.

[4]  Wilson W Wong,et al.  Synthetic biology in cell-based cancer immunotherapy. , 2015, Trends in biotechnology.

[5]  S. Perrin.  Preclinical research: Make mouse studies work , 2014, Nature.

[6]  Chunxiao Zhou,et al.  The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer , 2016, Oncotarget.

[7]  C. Marth,et al.  Why did p53 gene therapy fail in ovarian cancer? , 2003, The Lancet. Oncology.

[8]  Jun Chang,et al.  Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ(null) mice generates humanized mice that improve functional B cell development. , 2015, Clinical immunology.

[9]  Michele De Palma,et al.  The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities , 2012, Molecular oncology.

[10]  N. Dhomen,et al.  Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma. , 2016, Cancer discovery.

[11]  M. Beyer,et al.  TALEN-mediated genome engineering to generate targeted mice , 2015, Chromosome Research.

[12]  D. Hutmacher,et al.  Periosteum tissue engineering in an orthotopic in vivo platform. , 2017, Biomaterials.

[13]  C. Takimoto.  Why drugs fail: of mice and men revisited. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  Christopher J Tape,et al.  Systems Biology Analysis of Heterocellular Signaling. , 2016, Trends in biotechnology.

[15]  A. Pinto,et al.  Cre‐loxP‐Mediated Recombination: General Principles and Experimental Considerations , 2017, Current protocols in mouse biology.

[16]  L. Ellis,et al.  Cancer: The nuances of therapy , 2009, Nature.

[17]  E. Papapetrou.  Patient-derived induced pluripotent stem cells in cancer research and precision oncology , 2016, Nature Medicine.

[18]  Dietmar Werner Hutmacher,et al.  Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance. , 2015, Current opinion in biotechnology.

[19]  A. Palucka,et al.  Development and function of human innate immune cells in a humanized mouse model , 2014, Nature Biotechnology.

[20]  D. Greiner,et al.  Humanized mice for immune system investigation: progress, promise and challenges , 2012, Nature Reviews Immunology.

[21]  D. Quail,et al.  Microenvironmental regulation of tumor progression and metastasis , 2014 .

[22]  A. Reinisch,et al.  Generation and use of a humanized bone-marrow-ossicle niche for hematopoietic xenotransplantation into mice , 2017, Nature Protocols.

[23]  P. Friedl,et al.  Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response. , 2013, Current opinion in cell biology.

[24]  P. Bourgine,et al.  Engineering of a functional bone organ through endochondral ossification , 2013, Proceedings of the National Academy of Sciences.

[25]  C. Wells,et al.  Human CD141+ Dendritic Cell and CD1c+ Dendritic Cell Undergo Concordant Early Genetic Programming after Activation in Humanized Mice In Vivo , 2017, Front. Immunol..

[26]  Mina J. Bissell,et al.  Putting tumours in context , 2001, Nature Reviews Cancer.

[27]  T. Seyfried,et al.  On the origin of cancer metastasis. , 2013, Critical reviews in oncogenesis.

[28]  George M Church,et al.  Multiplexed Engineering in Biology. , 2016, Trends in biotechnology.

[29]  Andrew L. Kung,et al.  Examining the utility of patient-derived xenograft mouse models , 2015, Nature Reviews Cancer.

[30]  Ali Khademhosseini,et al.  Microengineered hydrogels for tissue engineering. , 2007, Biomaterials.

[31]  Hao Yin,et al.  CRISPR-mediated direct mutation of cancer genes in the mouse liver , 2014, Nature.

[32]  Samir J. Courdy,et al.  Patient‐Derived Models of Human Breast Cancer: Protocols for In Vitro and In Vivo Applications in Tumor Biology and Translational Medicine , 2013, Current protocols in pharmacology.

[33]  G. Mills,et al.  Personalized Preclinical Trials in BRAF Inhibitor–Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies , 2015, Clinical Cancer Research.

[34]  Fabrizio Gelain,et al.  Peptidic Biomaterials: From Self-Assembling to Regenerative Medicine. , 2017, Trends in biotechnology.

[35]  D. Hutmacher,et al.  A Validated Preclinical Animal Model for Primary Bone Tumor Research. , 2016, The Journal of bone and joint surgery. American volume.

[36]  Joshua M. Korn,et al.  High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response , 2015, Nature Medicine.

[37]  Peter W Zandstra,et al.  Engineering a humanized bone organ model in mice to study bone metastases , 2017, Nature Protocols.

[38]  Mark Tangney,et al.  Synthetic Biology in the Driving Seat of the Bioeconomy. , 2017, Trends in biotechnology.

[39]  M. Bissell,et al.  Tumor engineering: the other face of tissue engineering. , 2010, Tissue engineering. Part A.

[40]  Rudolf Jaenisch,et al.  One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering , 2013, Cell.

[41]  D. Adams,et al.  Intra- and inter-tumor heterogeneity in a vemurafenib-resistant melanoma patient and derived xenografts , 2015, EMBO molecular medicine.

[42]  A. Kulkarni,et al.  Generation of Transgenic Mice , 2009, Current protocols in cell biology.

[43]  E. Clair,et al.  The calm after the cytokine storm: lessons from the TGN1412 trial , 2008 .

[44]  Steven C. Wheelwright,et al.  Accelerating the Design‐build‐test Cycle for Effective Product Development , 1994 .

[45]  P. Kostenuik,et al.  Denosumab, a Fully Human Monoclonal Antibody to RANKL, Inhibits Bone Resorption and Increases BMD in Knock‐In Mice That Express Chimeric (Murine/Human) RANKL , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[46]  V. LeBleu,et al.  EMT Program is Dispensable for Metastasis but Induces Chemoresistance in Pancreatic Cancer , 2015, Nature.

[47]  H. Attarwala,et al.  TGN1412: From Discovery to Disaster , 2010, Journal of young pharmacists : JYP.

[48]  D. Strech,et al.  Animal Study Registries: Results from a Stakeholder Analysis on Potential Strengths, Weaknesses, Facilitators, and Barriers , 2016, PLoS biology.

[49]  I. Huijbers,et al.  Using the GEMM-ESC strategy to study gene function in mouse models , 2015, Nature Protocols.

[50]  C. Kuperwasser,et al.  Humanization of the mouse mammary gland. , 2015, Methods in molecular biology.

[51]  Yoon Young Choi,et al.  Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer , 2016, Scientific Reports.

[52]  Robert A. Weinberg,et al.  Comparative Biology of Mouse versus Human Cells: Modelling Human Cancer in Mice O P I N I O N , 2022 .

[53]  J. Clements,et al.  Tissue engineered humanized bone supports human hematopoiesis in vivo. , 2015, Biomaterials.

[54]  Anna V. Taubenberger,et al.  A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone , 2014, Clinical and Experimental Metastasis.

[55]  Jeremy Luban,et al.  Overcoming current limitations in humanized mouse research. , 2013, The Journal of infectious diseases.

[56]  Ciprian Catana,et al.  Simultaneous PET-MRI: a new approach for functional and morphological imaging , 2008, Nature Medicine.

[57]  Steve D. M. Brown,et al.  The mouse ascending: perspectives for human-disease models , 2007, Nature Cell Biology.

[58]  J. Pollard,et al.  Optical Windows for Imaging the Metastatic Tumour Microenvironment in vivo. , 2017, Trends in biotechnology.