Miguel Herrero - Academia.edu (original) (raw)

Papers by Miguel Herrero

PLoS ONE, 2014

Tumor heterogeneity is widely considered to be a determinant factor in tumor progression and in p... more Tumor heterogeneity is widely considered to be a determinant factor in tumor progression and in particular in its recurrence after therapy. Unfortunately, current medical techniques are unable to deduce clinically relevant information about tumor heterogeneity by means of non-invasive methods. As a consequence, when radiotherapy is used as a treatment of choice, radiation dosimetries are prescribed under the assumption that the malignancy targeted is of a homogeneous nature. In this work we discuss the effects of different radiation dose distributions on heterogeneous tumors by means of an individual cell-based model. To that end, a case is considered where two tumor cell phenotypes are present, which we assume to strongly differ in their respective cell cycle duration and radiosensitivity properties. We show herein that, as a result of such differences, the spatial distribution of the corresponding phenotypes, whence the resulting tumor heterogeneity can be predicted as growth proceeds. In particular, we show that if we start from a situation where a majority of ordinary cancer cells (CCs) and a minority of cancer stem cells (CSCs) are randomly distributed, and we assume that the length of CSC cycle is significantly longer than that of CCs, then CSCs become concentrated at an inner region as tumor grows. As a consequence we obtain that if CSCs are assumed to be more resistant to radiation than CCs, heterogeneous dosimetries can be selected to enhance tumor control by boosting radiation in the region occupied by the more radioresistant tumor cell phenotype. It is also shown that, when compared with homogeneous dose distributions as those being currently delivered in clinical practice, such heterogeneous radiation dosimetries fare always better than their homogeneous counterparts. Finally, limitations to our assumptions and their resulting clinical implications will be discussed.

PLOS Computational Biology, 2015

Tumor cells develop different strategies to cope with changing microenvironmental conditions. A p... more Tumor cells develop different strategies to cope with changing microenvironmental conditions. A prominent example is the adaptive phenotypic switching between cell migration and proliferation. While it has been shown that the migration-proliferation plasticity influences tumor spread, it remains unclear how this particular phenotypic plasticity affects overall tumor growth, in particular initiation and persistence. To address this problem, we formulate and study a mathematical model of spatio-temporal tumor dynamics which incorporates the microenvironmental influence through a local cell density dependence. Our analysis reveals that two dynamic regimes can be distinguished. If cell motility is allowed to increase with local cell density, any tumor cell population will persist in time, irrespective of its initial size. On the contrary, if cell motility is assumed to decrease with respect to local cell density, any tumor population below a certain size threshold will eventually extinguish, a fact usually termed as Allee effect in ecology. These results suggest that strategies aimed at modulating migration are worth to be explored as alternatives to those mainly focused at keeping tumor proliferation under control.

Discrete and Continuous Dynamical Systems - Series S, 2010

Physica A-statistical Mechanics and Its Applications - PHYSICA A, 2008

This paper is concerned with a quantitative model describing the interaction of three sociologica... more This paper is concerned with a quantitative model describing the interaction of three sociological species, termed as owners, criminals and security guards, and denoted by X, Y and Z respectively. In our model, Y is a predator of the species X, and so is Z with respect to Y. Moreover, Z can also be thought of as a predator of X, since this last population is required to bear the costs of maintaining Z. We propose a system of three ordinary differential equations to account for the time evolution of X(t), Y(t) and Z(t) according to our previous assumptions. Out of the various parameters that appear in that system, we select two of them, denoted by H, and h, which are related with the efficiency of the security forces as a control parameter in our discussion. To begin with, we consider the case of large and constant owners population, which allows us to reduce to a bidimensional system for Y(t) and Z(t). As a preliminary step, this situation is first discussed under the additional ass...