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Your search keyword '"Gatenby, R.A."' showing total 19 results
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19 results on '"Gatenby, R.A."'

6. Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer

Author

Zhang, J., Cunningham, J.J, Brown, J.S., and Gatenby, R.A.

Abstract

Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgenindependent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.

Published
2017

9. pH imaging

Author

Gillies, R.J., primary, Raghunand, N., additional, Garcia-Martin, M.L., additional, and Gatenby, R.A., additional

Published
2004
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15. Mathematical modelling of tumour acidity

Author

Smallbone, K., Gatenby, R.A., Maini, P.K., Smallbone, K., Gatenby, R.A., and Maini, P.K.

Abstract

Acid-mediated tumour invasion is receiving increasing experimental and clinical attention. Previous models proposed to describe this phenomenon failed to capture key properties of the system, such as the existence of the benign steady state, or predicted incorrectly the size of the inter-tissue gap. Here we show that taking proper account of quiescence ameliorates these drawbacks as well as revealing novel behaviour. The simplicity of the model allows us to fully identify the key parameters controlling different aspects of behaviour.

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