Why is cancer so common and why do cancers often become resistant to treatments? These are complex questions, but critical ones if we are to reduce the burden of the disease and improve outcomes. Key insights into these areas are now being provided by viewing cancer through the lens of a 150-year-old idea — Charles Darwin’s theory of evolution by natural selection. This is why we at The Institute of Cancer Research in London have set up our Centre for Evolution and Cancer – the first of its kind and scale in the world — led by Professor Mel Greaves FRS, a pioneer and leader in this field.
As Mel discusses in his wonderful book (1), cancer is part of our evolutionary legacy. Genetic diversity arrived at through mutation is the raw material for natural selection. Without diversity our species would not have been able to adapt and evolve, but the underlying mutation rate in cells can allow them to acquire the mutations that may turn them from a normal cell into a cancer cell.
Cancer may also be the price we pay for living on average almost twice as long as when humans first evolved. Most cancers occur in older people, most of whom would not have been alive in pre-historical times because life expectancy was so low. We know too that modern lifestyles considerably increase the incidence of cancer. For example, the risk of breast cancer in women is considerably reduced by having multiple children, particularly at a young age, and by extended periods of breast feeding. Women in pre-history were probably breast feeding or pregnant most of their post-pubescent years. That is very different to the modern-day situation, and the change in lifestyle has undoubtedly had an effect on the incidence of breast cancer. Of course we can’t turn the clock back, but working out why having children and breast feeding reduce risk could allow us to mimic whatever changes occur as a preventative strategy.
Many cancers may also have acquired the ability to evolve at a faster intrinsic rate by losing their ability to properly repair their DNA, increasing mutation rates. This cellular DNA damage can then be exacerbated by external forces such as the chemicals in cigarette smoke and the ultraviolet rays in sunlight. These factors conspire, leading to extensive genetic diversity as a tumour grows and spreads. In effect there is an evolutionary tree of cancers within a single individual and this diversity becomes very important when the patient is treated. Most cancer cells may be killed very well by some drugs, leading to a clinically observable response on a scan. However, the population of cells is so large and diverse that a cell may already exist that is resistant. Over time, this resistant cell will grow into a clone which will eventually dominate the tumour and result in relapse.
Our new Centre will contain experimental biologists, molecular pathologists, mathematicians and experts in drug discovery and development working together in a multi-disciplinary fashion. Potential approaches to improving outcomes and delaying or eliminating resistance to drugs include giving combinations of drugs and perhaps surprisingly stopping treatments that are working before resistance occurs and then re-initiating the same treatment later. There is still a tremendous amount to learn in this area and the ICR is now in the perfect position to apply that new knowledge.
1. Greaves, M. Cancer: The Evolutionary Legacy. Oxford University Press, Oxford (2000).
2. Greaves, M and Maley CC. Clonal Evolution in Cancer. Nature, 481: 306 (2012).