Cancer research today is highly specialised. Yet the disease itself is, of course, a multifaceted and multiscale disease – and there is no single explanation for how and why we get cancer.

Improvements in understanding and treating cancers will likely be aided by integrating specialist knowledge into more general biological principles, which can inform the specialist study of particular cancers.

An illustration of the above is the search for oncogenes – genes that, when mutated, give rise to cancer. Early enthusiasm for the oncogene research programme led many to expect that cancer could eventually be traced to a small number of genetic culprits that could potentially be blocked medically. Though naïve in retrospect, this approach fit the prevailing assumption among many biologists that for any trait, process, or disease, there should be a small number of genes that controls it.

Many such genes with major effects have been found, but much subsequent research has revealed that genetic causes tend to be more distributed, dynamic, and context-dependent than previously imagined. Genes rarely have large effects on biological function in isolation; instead, they operate within larger networks of many genes that actively regulate each other and respond to chemical and physical signals from other cells. In many cases, these gene networks harbour redundancy and have evolved to be robust, maintaining their overall function despite mutations in their components. This can potentially explain why adults have much lower cancer rates than one might expect from the rapid accumulation of somatic mutations that occurs over a lifetime.

The context-dependence of genetic effects also means that a given gene or chemical signal is not necessarily cancer-causing or cancer-protective by itself: the same molecule may be beneficial, harmful, or neutral depending on its cellular context.

The need for a wide lens

While the study of individual genes and molecular pathways has generated important insights, there is progress to be made in understanding cancer by integrating the effects of many genes and their cell and tissue contexts. This work of integration can be aided by incorporating ideas from areas of fundamental biology outside of cancer research.

An example is the relevance of evolutionary and developmental biology for answering the question – why are many cancers so effective at proliferating, resisting treatment, and evading the immune system? Part of the answer is that cancers undergo a process of Darwinian natural selection within the body, in which cancer cells having proliferative or immune-evading features outcompete and replace those that don’t.

Yet many of the complex adaptations cancer seems to possess – such as metastasis – do not originate de novo on such short time scales. Instead, processes like metastasis involve re-activating existing genetic programmes that are necessary and adaptive for biological development in the womb. Some cancer researchers have noticed that adult cancer cells express genes normally expressed only during foetal development. This is a version of a process known more generally in evolutionary-developmental biology as co-option, or the re-deployment of existing genetic mechanisms into a new time or place in the body.

Most hallmarks of cancer involve the co-option of processes that are normally beneficial, such as wound-healing, vascularisation, and proliferative signalling into new contexts where they no longer self-attenuate. This conceptual link from developmental biology to cancer research generates the insight that where human development and physiology is dependent on those beneficial processes, then those processes are potentially co-optable by cancer.

Furthermore, natural selection acts more intensely on the early processes generating a viable individual capable of reproducing, than it does later in life. So the evolutionary forces that maintain early developmental processes needed for reproduction will be stronger than the forces that protect against cancerous co-option of those processes later in life.

Helpful for developing treatments?

Understanding is the first step in designing effective interventions, and this is where the existing wealth of fundamental knowledge about how these processes work can be deployed in service of cancer research.

Creating synergy between medical research and basic biological research was of course one of the goals behind the founding of the Francis Crick Institute, where I lead a research laboratory. My lab doesn’t study cancer directly but instead focuses on understanding how developmental processes have evolved.

This work intersects with cancer research at the level of concepts and principles, such as co-option, robustness of gene networks, and the adaptive pressures faced by different developmental stages. Engagement with concepts and principles like these is important for both clinical and basic research as it allows us to integrate information across seemingly unrelated areas, which is often a source of novel scientific ideas.

Yet engaging with concepts and principles can quickly become highly abstract and even philosophical. For example: how should we define co-option so that the concept captures interesting similarities across cancer biology and evolutionary biology? How is it that cancer occurrence can have explanations at multiple levels or scales? How should we understand the seemingly purposive and malevolent behaviours exhibited by cancer cells?

This is where my background in philosophy of science is useful for disentangling definitions and understanding the implications of the concepts we use. Combining conceptual thinking and hands-on research goes beyond what can be done with either approach separately, and facilitates integrating specialist knowledge into the big picture.