Month: January 2022

Transition Therapy: Tackling the Ecology of Tumor Phenotypic Plasticity

Guim Aguadé-Gorgorió, Stuart Kauffman & Ricard Solé 

Bulletin of Mathematical Biology volume 84, Article number: 24 (2022)

Phenotypic switching in cancer cells has been found to be present across tumor types. Recent studies on Glioblastoma report a remarkably common architecture of four well-defined phenotypes coexisting within high levels of intra-tumor genetic heterogeneity. Similar dynamics have been shown to occur in breast cancer and melanoma and are likely to be found across cancer types. Given the adaptive potential of phenotypic switching (PHS) strategies, understanding how it drives tumor evolution and therapy resistance is a major priority. Here we present a mathematical framework uncovering the ecological dynamics behind PHS. The model is able to reproduce experimental results, and mathematical conditions for cancer progression reveal PHS-specific features of tumors with direct consequences on therapy resistance. In particular, our model reveals a threshold for the resistant-to-sensitive phenotype transition rate, below which any cytotoxic or switch-inhibition therapy is likely to fail. The model is able to capture therapeutic success thresholds for cancers where nonlinear growth dynamics or larger PHS architectures are in place, such as glioblastoma or melanoma. By doing so, the model presents a novel set of conditions for the success of combination therapies able to target replication and phenotypic transitions at once. Following our results, we discuss transition therapy as a novel scheme to target not only combined cytotoxicity but also the rates of phenotypic switching.

Read the full article at: link.springer.com

Magnitude-sensitivity: rethinking decision-making

The cover of the January issue of the magazine Trends in Cognitive Sciences shows a human brain composed of a honeybee swarm. The artwork depicts two seemingly distant biological systems that present striking similarities in decision dynamics and properties of information processing. Inspired by the study of house-hunting honeybees, recent research has established that performance in decision-making is affected in predictable ways by the overall goal-relevant magnitude of the alternatives. Magnitude-sensitivity has been observed in humans performing a wide variety of tasks and in organisms as diverse as non-human primates and aneural slime molds. Angelo Pirrone and colleagues review the literature and highlight how prominent accounts of theoretical, descriptive, and normative decision-making had to be revisited to explain magnitude-sensitivity.
A. Pirrone, A. Reina, T. Stafford, J.A.R. Marshall, F. Gobet. Magnitude-sensitivity: rethinking decision-making. Trends in Cognitive Sciences 26(1), 2022. https://doi.org/10.1016/j.tics.2021.10.006

Read the full article at: www.sciencedirect.com

The Great 1976 Tangshan Earthquake: Learning from the 1966-1976 Chinese Prediction Program

Euan Mearns and Didier Sornette

From 1966 to 1976, four large earthquakes shook the Bohai Bay rift basin of Northeast China. This prompted the Chinese to launch one of the world’s largest social and science experiments into earthquake prediction that would engage tens of thousands of common people. The climax of this came in February 1975 where a prediction was made hours before the Haicheng earthquake struck. Evacuation of the city of Yingkou and some rural districts saved thousands of lives. The Chinese were jubilant, believing they had cracked the earthquake prediction conundrum. Eighteen months later, however, on the 28th July, 1976, jubilation turned to despair when a great earthquake flattened the large industrial city of Tangshan resulting in 250,000 to 650,000 casualties. This book describes the geological, technical, political and sociological backgrounds to the Haicheng prediction success and the Tangshan prediction failure.
Ahead of the Tangshan earthquake, Chinese seismologists had accumulated significant information that suggested an earthquake was imminent and came close to making a prediction. With improved knowledge and vastly improved ability to accumulate, consolidate and analyse data, this book suggests that Tangshan could have been predicted today using techniques developed in China in that epic decade of discovery. Building on these insights, it also offers a viable future pathway towards earthquake predictions that combines the insights and organisation of the 1966-1976 Chinese prediction program with modern technologies, in order to facilitate data gathering, interpretation and sharing.

More at: www.cambridgescholars.com