2018
DOI: 10.1101/381418
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Modelling bistable tumour population dynamics to design effective treatment strategies

Abstract: Despite recent advances in targeted drugs and immunotherapy, cancer remains "the emperor of all maladies" due to inevitable emergence of resistance. Drug resistance is thought to be driven by mutations and/or dynamic plasticity that deregulate pathway activities and regulatory programs of a highly heterogeneous tumour. In this study, we propose a modelling framework to simulate population dynamics of heterogeneous tumour cells with reversible drug resistance. Drug sensitivity of a tumour cell is determined by … Show more

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Cited by 2 publications
(2 citation statements)
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“…Careful experiments need to be set up to discriminate between the two possible mechanisms, as they may have different implications for how a more optimal treatment would be designed. Positive clinical results for evolutionary-guided therapies remain confounded by other potential mechanisms driving them, including the effect of intermittent scheduling on the intratumoral vasculature, 79 , 80 reversible gene expression profiles affecting drug resistance of a single subclone, 81 or the immune system. 82 - 85 The uncertainty about correct model assumptions is termed uncertainty about “model topology.” FQM attempts to do a sensitivity analysis across multiple model topologies.…”
Section: Coping With Uncertaintymentioning
confidence: 99%
“…Careful experiments need to be set up to discriminate between the two possible mechanisms, as they may have different implications for how a more optimal treatment would be designed. Positive clinical results for evolutionary-guided therapies remain confounded by other potential mechanisms driving them, including the effect of intermittent scheduling on the intratumoral vasculature, 79 , 80 reversible gene expression profiles affecting drug resistance of a single subclone, 81 or the immune system. 82 - 85 The uncertainty about correct model assumptions is termed uncertainty about “model topology.” FQM attempts to do a sensitivity analysis across multiple model topologies.…”
Section: Coping With Uncertaintymentioning
confidence: 99%
“…Mathematical modeling has been and continues to be employed to understand the underlying dynamics, to help formalize hypotheses, and to evaluate and improve treatment options ( 3 5 ). This is critically important in immuno-oncology, where clinicians must consider the tumor’s response to therapy as well as the immune system’s ( 4 , 6 , 7 ).…”
Section: Introductionmentioning
confidence: 99%