"A conceptual cancer development model with time-varying extinction threshold: Breast cancer case study"Bastian, FrankWe propose a conceptual model of cancer development that captures both carcinogenesis and subsequent cancer progression. One of the central concepts of the model is an extinction threshold akin to the strong Allee effect in population biology. First, we uncover limitations of the commonly used strong Allee effect model, initially proposed by Vito Volterra, to reproduce typical cancer progression. Addressing these limitations, we propose a new cancer progression model with different forms of cancer progression above the extinction threshold ranging from logistic to Gompertzian growth. Second, we propose a cancer development model that incorporates three processes: (i) random mutations of stem cells at a rate that can increase over time due to ageing, (ii) cancer suppression mechanisms whose strength can also change over time, giving rise to a time-varying extinction threshold, and (iii) our new proposed progression model. Using tuned parameters and breast cancer as a case study, we show that our model reproduces typical cancer progression, generates testable predictions, and gives new insight into observed non-trivial cumulative lifetime risk for breast cancer. |
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