Colon cancer, mathematical time travel, and questioning the sequential mutation model.

On Saturday, I arrived in Columbus, Ohio for the the MBI Workshop on the Ecology and Evolution of Cancer. Today, our second day started. The meeting is an exciting combination of biology-minded mathematicians and computer scientists, and math-friendly biologist and clinicians. As is typical of workshops, the speakers of the first day had an agenda of setting the scope. In this case, the common theme was to question and refine the established model as embodied by Hannah & Weinberg’s (2000) hallmarks of cancer outlined. For an accessible overview of these hallmarks, I recommend Buddhini Samarasinghe’s series of posts. I won’t provide a full overview of the standard model, but only focus on the aspects at issue for the workshop participants. In the case of the first two speakers, the standard picture in question was the sequential mutation model. In the textbook model of cancer, a tumour acquires the hallmark mutations one at a time, with each subsequent mutation sweeping to fixation. Trevor Graham and Darryl Shibata presented their work on colon cancer, emphasizing tumour heterogeneity, and suggesting that we might have to rewrite the sequential mutation page of our Cancer 101 textbooks to better discuss the punctuated model.
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