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Exploiting evolution to treat drug resistance: Combination therapy and the double bind Nature Precedings
David Basanta; Robert Gatenby; Alexander R. A. Anderson.
Although many anti cancer therapies are successful in killing a large percentage of tumour cells when initially administered, the evolutionary dynamics underpinning tumour progression mean that often resistance is an inevitable outcome, allowing for new tumour phenotypes to emerge that are unhindered by the therapy. Research in the field of ecology suggests that an evolutionary double bind could be an effective way to treat tumours. In an evolutionary double bind two therapies are used in combination such that evolving resistance to one leaves individuals more susceptible to the other. In this paper we present a general evolutionary game theory model of a double bind to study the effect that such approach would have in cancer. Furthermore we use this...
Tipo: Manuscript Palavras-chave: Cancer; Ecology; Pharmacology; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6380/version/1
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Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game Nature Precedings
David Basanta; Jacob G. Scott; Mayer N. Fishman; Gustavo E. Ayala; Simon W. Hayward; Alexander R. A. Anderson.
BACKGROUND: Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under appreciated therapeutic target. We use observations of primary tumor biology from prostate cancer to extrapolate a mathematical model: specifically; it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent - in this case the local stromal cells may act to restrain the growth of the...
Tipo: Manuscript Palavras-chave: Cancer; Pharmacology; Bioinformatics; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6385/version/1
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