Sunday, April 24, 2016

Toxicity Management in CAR T cell therapy for B-ALL: Mathematical modelling as a new avenue for improvement

Toxicity Management in CAR T cell therapy for B-ALL: Mathematical modelling as a new avenue for improvement.

Thursday, April 21, 2016

Universal asymptotic clone size distribution for general population growth

Universal asymptotic clone size distribution for general population growth


Deterministically growing (wild-type) populations which seed stochastically developing mutant clones have found an expanding number of applications from microbial populations to cancer. The special case of exponential wild-type population growth, usually termed as the Luria-Delbruck or Lea-Coulson model, is often assumed but seldom realistic. In this article we generalise the model to different types of wild-type population growth, with mutants evolving as a birth-death branching process. Our focus is on the size distribution of clones after some time, which can be mapped to the total number of mutants. Exact expressions are derived for exponential, power-law and logistic population growth. We prove that the large time limit of the clone size distribution has a general two-parameter form for a large class of population growth. The large time clone size distribution always has a power-law tail, and for subexponential wild-type growth the probability of a given clone size is inversely proportional to the clone size. We support our results by analysing a data-set on tumour metastasis sizes, and we find that a power-law tail is more likely than an exponential one, in agreement with our predictions.

Tuesday, April 19, 2016

Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights

Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silica insights


There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve functional tumour-associated blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation medi- ated by vascular targeting agents that induce occlusion/collapse of tumour blood vessels. In contrast, the therapeutic intention of normalising the abnormal structure and function of tumour vascular net- works, e.g. via alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and radiation therapy efficacy. Although both strategies have shown therapeutic potential, it remains unclear why they often fail to control glioma invasion into the surrounding healthy brain tissue. To shed light on this issue, we propose a mathematical model of glioma invasion focusing on the interplay between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells and modulations of the functional tumour vasculature. Vaso-modulatory interventions are modelled by varying the degree of vaso-occlusion. We discovered the existence of a critical cell proliferation/diffusion ratio that separates glioma invasion re- sponses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the tumour front speed and increase the infiltration width, for those in the other regime the invasion speed increases and infiltration width decreases. We show how these in silico findings can be used to guide individualised approaches of vaso-modulatory treatment strategies and thereby improve success rates.

Link:arXiv:1604.05082http://arxiv.org/abs/1604.05082