Is genome instability the key to fighting cancer?

Cancer is the result of a series of genomic alterations of normal cells that allow them to escape cell controls and proliferate uncontrollably. Thus, the cooperation that maintains the integrity of a multicellular organism is broken, and the accumulation of further changes or mutations in the population generated by these abnormal cells can lead to the growth of malignant tumours, which can cause death. From an evolutionary standpoint, tumour progression is a microevolutionary process in which tumours must overcome selective barriers imposed by the body or therapies.

Today, there has been much progress in the treatment of some types of cancer, but the frequency of uncured tumours has not changed in the last 50 years. Using evolutionary arguments, in recent decades scientific theorists have been discussing the need to focus on this problem from a different perspective: a new integrative vision that takes into account the Darwinian and ecological nature of the disease.

Theoretical models that help to find better therapeutic strategies

The Complex Systems Laboratory directed by Ricard Solé, ICREA researcher at the Department of Experimental and Health Sciences (CEXS) and researcher at the Institute of Evolutionary Biology (UPF-CSIC) and of the Santa Fe Institute in the USA, has developed a line of research on theoretical and computational oncology.

As commented by Josep Sardanyés, member of the Complex Systems Laboratory, "we are interested in an important aspect of cancer: its huge levels of genome instability". In most advanced tumours, there are high levels of genome instability at the karyotype, where you can see duplicated, lost or broken chromosomes in apparently disordered patterns. And, Sandanyés continues, "despite this high level of aneuploidy, cancer cells are capable of adapting and spreading themselves through metastasis. Our laboratory poses whether there are limits to the high degree of genome instability and how this phenomenon may be modelled".

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In recent years, members of the Complex Systems Laboratory have published several studies on the processes of tumour microevolution and competition using theoretical models. Ricard Solé, together with Tomas Deisboeck put forward a minimum model of genome instability. Now, an extension of this mathematical model is published in Computational and Applied Mathematics in a study led by Josep Sardanyés , researcher at the Institute of Evolutionary Biology (UPF-CSIC) and of the Department of Experimental and Health Sciences (CEXS) at UPF, in which he has characterized the effects of increasing genome instability in tumour cell populations, as well as their response time.

"We have seen that the population of tumour cells can be forced towards small and controlled populations increasing their mutation rate, and that the time required for achieving this state is short. Currently targeted therapy methods are being developed for tumour cells", said Sardanyés. Thus, this therapeutic strategy would enable detecting cancer cells and releasing (mutagenic) drugs within these cells, selectively.

These results show that mathematical modelling and computational biology enable deepening our understanding of the behaviour of tumour systems and making predictions that can be highly useful with a view to future therapies and strategies to fight cancer.

Reference work:

Vanessa Castillo, J. Tomás Lázaro and Josep Sardanyés (2015), " Dynamics and bifurcations in a simple quasispecies model of tumorigenesis" , Computational and Applied Mathematics, arXiv:1411.6531 [math.DS]