F438A2FEd01 - REVIEWS Maximizing mouse cancer models...

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Cancer represents an increasing cause of morbidity and mortality throughout the world as health advances con‑ tinue to extend the life spans of our populations. Although our basic understanding of cancer has increased consid‑ erably since 1971, when United States President Richard Nixon initiated the ‘War on Cancer’, our ability to trans‑ late this knowledge into a health benefit for patients has been restricted to certain malignancies and often only temporarily. Importantly, specific hypotheses developed from our knowledge of cancer biology can be tested in increasingly complex model systems ranging from cell culture to genetically engineered mouse models, and such investigations should prove invaluable in discover‑ ing new methodologies for the detection, management and treatment of cancer in humans. The evolution of cancer modelling The laboratory mouse ( Mus musculus ) is one of the best model systems for cancer investigations owing to various factors including its small size and propensity to breed in captivity, lifespan of 3 years, extensive physi‑ ological and molecular similarities to humans, and an entirely sequenced genome. M. musculus cancer models have progressed through several phases of increasing complexity, including xenograft tumours derived from tumour cell lines or explants, chemical and viral car‑ cinogens, and several variations of genetically engineered mice (GEM). Each approach has its own advantages and disadvantages, and it is important to choose the most appropriate system for particular questions. Tissue culture and ‘animal culture’ The establishment of cell lines from human and animal tumours is largely responsible for our early progress in cancer research. For example, these studies led to the description and ultimate discovery of transforming genes, thereby laying the groundwork for the field of cancer biology and cell biology. However, many of our initial observations are now being re‑evaluated owing to our recent appreciation of cancer as a complex disease with intricate interactions between transformed cells that harbour oncogenic mutations (commonly referred to as the cell autonomous compartment) and surrounding non-cell autonomous constituents, such as normal cells, stromal cells and immune cells 1 . Indeed, several facets of tumorigenesis, including angiogenesis and metastasis, are not possible to assess in cell culture. Improvements in tissue sampling, genomics and biostatistics have enabled the direct characterization of primary human tumours; however, these analyses are limited and still do not take into account the contributions of the entire body. The development of xenograft models enabled the rapid and facile in vivo assessment of tumour tissue and cell lines in immunocompromised mice 2 . Indeed, patient‑specific models have recently been proposed as a means to prospectively personalize treatment regimens 3,4 . However, several crucial differences exist when comparing tumour xenografts with patient‑
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This note was uploaded on 05/28/2010 for the course WE MOBI000000 taught by Professor Geertberx during the Spring '10 term at Ghent University.

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F438A2FEd01 - REVIEWS Maximizing mouse cancer models...

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