The Universality of Cancer

Carson C. Chow, Yanjun Li, Vipul Periwal

Cancer has been characterized as a constellation of hundreds of diseases differing in underlying mutations and depending on cellular environments. Carcinogenesis as a stochastic physical process has been studied for over sixty years, but there is no accepted standard model. We show that the hazard rates of all cancers are characterized by a simple dynamic stochastic process on a half-line, with a universal linear restoring force balancing a universal simple Brownian motion starting from a universal initial distribution. Only a critical radius defining the transition from normal to tumorigenic genomes distinguishes between different cancer types when time is measured in cell–cycle units. Reparametrizing to chronological time units introduces two additional parameters: the onset of cellular senescence with age and the time interval over which this cessation in replication takes place. This universality implies that there may exist a finite separation between normal cells and tumorigenic cells in all tissue types that may be a viable target for both early detection and preventive therapy.

http://arxiv.org/abs/1506.00597v1

Cancer therapeutic potential of combinatorial immuno- and vaso-modulatory interventions

Cancer therapeutic potential of combinatorial immuno- and vaso-modulatory interventions 

H. Hatzikirou, J. C. L. Alfonso, S. Muhle, C. Stern, S. Weiss, M. Meyer-Hermann

Currently, most of the basic mechanisms governing tumor-immune system interactions, in combination with modulations of tumor-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumor growth, where the main novelty is the modelling of the interplay between functional tumor vasculature and effector recruitment dynamics. Parameters are calibrated on the basis of different in vivo Rag1-/- and wild-type (WT) BALB/c murine tumor growth experiments. The model analysis supports that vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immuno-stimulation. We find that improved levels of functional vasculature, potentially mediated by vascular normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumor burden reduction and control. Normalization of tumor blood vessels opens a therapeutic window of opportunity to augment the anti- tumor immune responses, as well as to reduce the intratumoral immunosuppression and hypoxia due to vascular abnormalities. The potential success of normalizing tumor vasculature closely depends on the effector cell recruitment dynamics and tumor sizes. Furthermore, an arbitrary increase of initial effector cell concentration does not necessarily imply tumor control, and we evidence the existence of an optimal effector concentration range for tumor shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immune- and vaso-modulatory interventions.

http://arxiv.org/abs/1505.05670

A pan-cancer signature of neutral tumor evolution

Andrea Sottoriva , Trevor Graham 

 

Despite extraordinary efforts to profile cancer genomes on a large scale, interpreting the vast amount of genomic data in the light of cancer evolution and in a clinically relevant manner remains challenging. Here we demonstrate that cancer next-generation sequencing data is dominated by the signature of growth governed by a power-law distribution of mutant allele frequencies. The power-law signature is common to multiple tumor types and is a consequence of the effectively-neutral evolutionary dynamics that underpin the evolution of a large proportion of cancers, giving rise to the abundance of mutations responsible for intra-tumor heterogeneity. Importantly, the law allows the measurement, in each individual cancer, of the in vivo mutation rate and the timing of mutations with remarkable precision. This result provides a new way to interpret cancer genomic data by considering the physics of tumor growth in a way that is both patient-specific and clinically relevant.

 

bioRXiv: http://biorxiv.org/content/early/2015/02/11/014894