Evolutionarily stable anti-cancer therapies by autologous cell defection

Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Background and objectives: Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. Methodology: The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. Results: A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Conclusions and implications: Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under certain conditions. This method, named autologous cell defection, can be carried out using existing molecular biology and cell therapy techniques

Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies

Background: Tumour heterogeneity is documented for many characters, including the production of growth factors, one of the hallmarks of cancer. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment, as drugs that target growth factors are susceptible to the evolution of resistance. Methods: I use evolutionary game theory to model collective interactions between cancer cells, to analyse the dynamics of the production of growth factors and the effect of therapies that reduce their amount. Results: Five types of dynamics are possible, including the coexistence of producer and non-producer cells, depending on the production cost of the growth factor, on its diffusion range and on the degree of synergy of the benefit it confers to the cells. Perturbations of the equilibrium mimicking therapies that target growth factors are effective in reducing the amount of growth factor in the long term only if the reduction is extremely efficient and immediate. Conclusion: Collective interactions within the tumour can maintain heterogeneity for the production of growth factors and explain why therapies like anti-angiogenic drugs and RNA interference that reduce the amount of available growth factors are effective in the short term but often lead to relapse. Alternative strategies for evolutionarily stable treatments are discussed

Are the media globalizing political discourse? The war on terrorism case study

The paper challenges the claim that an increasingly global media is creating a homogenisation of political discourses at the international level. In particular, it explores the extent to which the U.S. government managed to affect global perceptions of the War On Terrorism through the media in the immediate aftermath of the 9/11 events. The research starts from the consideration that the U.S. government created, through the repetition of consistent messages, a very specific interpretation of the 9/11 events (a War On Terrorism frame) and attempted to export it globally in order to support its own foreign policy objectives. The analysis then focuses on the comparison between the War On Terrorism frame as delivered by the U.S. government and its reproduction within both the political and media discourses in a range of local cases at the international level. They include the U.S., France, Italy and Pakistan. The research questions current literature on globalisation by drawing on political communications’ framing theory. More specifically, it suggests first that there is no evidence of an on-going globalisation of either political or media discourses; secondly that the local nation-state level plays a key role in understanding the mechanisms of frames’ spreading at the global level; and thirdly that national culture is a major determinant in defining local political and media discourses’ contents, even in presence of a strong persuasion attempt by a powerful international actor such as the U.S. government

A multidisciplinary understanding of news: Comparing elite press framing of 9/11 in the US, Italy, France and Pakistan

Political Communications, International Communications, News Sociology, all claim to offer an explanation for what shapes the news, but provide extremely different, if not contradictory suggestions. Political communications almost takes for granted the fact that official actors have a major role in shaping news stories at the national level. International Communications points at several possibilities: structural economic imbalances lead to unidirectional news flows from rich countries towards poor countries; globalization causes news to become homogenised on a worldwide scale; news is geared to the tastes of local audiences by national news producers. News sociology, instead, argues that the news product of each media organization is the unique output of patterns of social interactions among media professionals. An international comparative study of the elite press framing of 9/11 in the US, Italy, France, and Pakistan reveals the limits of these approaches: none of them alone is able to explain the patterns of news contents that were detected in the empirical investigation.The analysis suggests that the content of press coverage in the newspapers under analysis is more effectively explained in terms of selection of newsworthy sources, guided by national interest, journalistic culture, and editorial policy. The study points to the benefit of adopting international comparative research designs and fundamentally argues that, if we want to explain news in the information age, we need to approach its study in a multidisciplinary perspective

Rebranding terror

Ten years after its most devastating attack, al-Qaeda has turned into a franchiser, publisher, and occasional climate-change activist. Can the world’s most deadly terrorist group go mainstream and keep its edge

Unamerican Views: Why US-developed models of press-state relations don't apply to the rest of the world

The article shows the limitations of the 'indexing' hypothesis, an influential conceptualization of state-press relations based on the notion that the media tend to reproduce the range of debate within political elites. The hypothesis, as confirmed by an international comparative investigation of the elite press coverage of 9/11 in the US, Italy, France, and Pakistan, cannot be applied outside the American context. The analysis finds that the variation in the levels of correlation between elite press coverage and governmental discourse are explained by previously neglected variables: national interest, national journalistic culture, and editorial policy within each media organization. The article argues that more international comparative research and multidisciplinary approaches are needed in order to renew old paradigms, especially at a time when the distinction between foreign and domestic politics is disappearing