I recently found myself in the Oxford Blackwells’ Norrington Room browsing the shelves for some holiday reading. One book in particular caught my eye, a blend of evolution — a topic that has long interested me — and cancer biology, a topic I’m increasingly exposed to in immune repertoire analysis collaborations but on which I am assuredly “non-expert”!
The Cheating Cell by Athene Aktipis provides a theoretical framework for understanding cancer by considering it as a logical sequitor of the advent of successful multicellular life.
Cancer often results from mutations leading to a local exploitation of entirely natural ‘overactivity’. For example, cells need to go into overdrive in a coordinated way at various times of life, such as to enable foetal development or perform efficient cellular repair. The body has also evolved to tolerate somatic mutation in some contexts, such as in the adaptive immune system, to enable bespoke responses to a wide range of pathogens. The evolutionary costs of precluding such processes in the body are simply too great.
Therefore, we have retained these crucial chemical mechanisms, despite them positioning us on the precipice of cancer, instead evolving regulatory elements (e.g. the commonly-studied TP53 gene) that seek to spot when cells are going out of control. But these regulatory genes have to strike the balance between letting the body loose when necessary and clamping down on activity when a cell is being exploitative. Having more copies of a regulatory gene leads to tighter cellular restriction, and a concurrent reduction in cancer probability, but also reduces the speed of cellular growth/repair and lowers fertility. The book dives into a range of examples from across the plant and animal kingdoms.
A fascinating observation is that often the maternal epigenome appears to prime towards the expression of regulatory elements, while the paternal epigenome does the opposite; potential reasons for why this phenomenon has evolved are explored in Chapter 4.
The book also considers how cancer develops once it has arisen, including the evolutionary/ecological drive towards further mutation to create a heterogenous tumour population (which may lead to cooperativity) and to metastasise, particularly upon depletion of the resources in the tumour microenvironment.
Chapter 7 concludes by considering how the concepts introduced in the previous chapters are being exploited by drug developers to design the next generation of cancer medication. A striking theme is that our mentality may need to shift away from tumour eradication and towards sustained control.
I’ve tried not to give too much away in this blog post, as I don’t want to spoil the book for those who haven’t yet read it! But suffice to say I found this a very instructive read and believe it offers an insightful perspective on how we will tackle cancer in the coming decade.
