Cancer: Off by a whisker

  title={Cancer: Off by a whisker},
  author={Carina Dennis},
  • C. Dennis
  • Published 16 August 2006
  • Medicine
  • Nature
Much of what we know about cancer comes from studying mice, and potential therapies are tested in the animals. But the differences between the species can scupper the best laid plans of researchers and drug companies, reports Carina Dennis. 
Rational Drug Design of Small Molecule Anticancer Agents: Preclinical Discovery
This chapter reviews the development of small molecule inhibitors that act on targets involved in the causation and progression of human cancer and reviews the technologies that are being implemented to improve the success rate and increase the speed of preclinical oncology drug development.
Mighty, But How Useful? The Emerging Role of Genetically Engineered Mice in Cancer Drug Discovery and Development
To date, the most pronounced impact that GEMMs have had on the biomedical industry has been in the areas of target and pathway validation, disease history elucidation, and the discovery and refinement of pharmacodynamic and toxicity biomarkers.
An Industry Perspective on the Utility of Short-Term Carcinogenicity Testing in Transgenic Mice in Pharmaceutical Development
Preliminary findings indicate that prediction of two-year rat bioassay outcomes based on data from chronic rat toxicity studies, together with early assessment of carcinogenic potential in short-term transgenic models, may have the potential to increase the timeliness and efficiency of strategies for the identification of human carcinogenic hazards.
Preclinical pharmacology and in vivo models
It is to be anticipated that the continued and increased consideration of pharmacology and appropriate in vivo models in the preclinical discovery phase of cancer drug development will result in a lower failure rate of molecules than hitherto in the later phases of clinical development, and, moreover, a new generation of better drugs to combat this all too common disease.
Are animal models predictive for humans?
The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes.
Guidelines for the welfare and use of animals in cancer research
New guidelines on the welfare and use of animals in cancer research are provided, including recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models and humane endpoints.
Human Stakeholders and the Use of Animals in Drug Development
It is proposed that the U.S. Food and Drug Administration (FDA) and Congress should work together to abolish regulations and policies that require animal use, to benefit pharmaceutical industry stakeholders, including patients whose health depends on drugs and the many people who rely on the financial well-being of pharmaceutical firms.
Murine models of chronic lymphocytic leukaemia: role of microRNA‐16 in the New Zealand Black mouse model
Exogenous restoration of miR‐16 to an NZB malignant B‐1 cell line resulted in cell cycle alterations, suggesting that the altered expression of Mirn15a/16‐1 is an important molecular lesion in CLL.
Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners
A highly reproducible in vitro three-dimensional tumor model for micrometastatic ovarian cancer (OvCa) is developed, which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens.
MicroRNA expression in canine mammary cancer
Because the dog presents with distinct, spontaneously occurring mammary tumors, it may serve as a model for genetic analysis and treatments of humans with malignant breast tumors and expression patterns of ten miRNAs known to be associated with human breast cancers were compared.


Comparative biology of mouse versus human cells: modelling human cancer in mice
There are fundamental differences in how the process of tumorigenesis occurs in mice and humans, and these differences affect the use of mice as models of human tumour pathogenesis.
Model organisms: The mighty mouse: genetically engineered mouse models in cancer drug development
The established uses and limitations of xenograft mouse models for cancer drug development are discussed, and the opportunities and challenges in the application of novel genetically engineered mouse models that more faithfully mimic the genetic and biological evolution of human cancers are described.
Comparative Oncogenomics Identifies NEDD9 as a Melanoma Metastasis Gene
Genomes of human cancer cells are characterized by numerous chromosomal aberrations of uncertain pathogenetic significance. Here, in an inducible mouse model of melanoma, we characterized metastatic
Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic Approach
A tractable model of liver cancer is established, two oncogenes that cooperate by virtue of their coamplification in the same genomic locus are identified, and an efficient strategy for the annotation of human cancer genes is suggested.
Cytochrome P450 and xenobiotic receptor humanized mice.
  • F. Gonzalez, A. Yu
  • Biology, Medicine
    Annual review of pharmacology and toxicology
  • 2006
In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development.
Neonatal sunburn and melanoma in mice
A genetically engineered mouse model is used to show that a single dose of burning ultraviolet radiation to neonates, but not adults, is necessary and sufficient to induce tumours with high penetrance which are reminiscent of human melanoma.
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
It is shown that mice carrying mutations in the tumour suppressor gene p53 were highly predisposed to a range of tumour types, predominantly early onset lung cancer.
Use of human tissue to assess the oncogenic activity of melanoma-associated mutations
Multiple genetic alterations occur in melanoma, a lethal skin malignancy of increasing incidence. These include mutations that activate Ras and two of its effector cascades, Raf and phosphoinositide
An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis
A method for comparing mouse models of cancer with human tumors using gene-expression profiling was applied to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model.
Can the pharmaceutical industry reduce attrition rates?
The pharmaceutical industry faces considerable challenges, both politically and fiscally, and the fiscal pressures that face the industry from the perspective of R&D are dealt with.