“Nothing in biology makes sense except in the light of evolution.”
Theodosius Dobzhanski, (1973)
Cancer is the second leading cause of death in the US1. With an aging population, cases of cancer are only expected to increase in the future. To combat cancer, the White House has recently announced a one billion dollar investment in cancer research. Clearly, cancer is a huge problem confronting humanity and thus a fundamental understanding of cancer is essential. Maybe the most fundamental question is: why does cancer exist? The answer is evolution by natural selection.
Evolution by natural selection occurs when organisms acquire mutations that alter their fitness (increase their reproductive success). An increase in fitness means that mutations are being passed on to offspring, whereas decreases in fitness lead to a loss of specific mutations from the gene pool. For instance, a single-celled organism that acquires mutations that allows it to out-compete other organisms will increase in population. In this case, selfish mutations are beneficial for the species’ survival.
At some point during evolution, single-celled organisms came together to form multi-cellular organisms. Multi-cellular organisms contain specialized cells for performing specific functions for the benefit of the entire organism. In certain historical situations, multi-cellular organisms must have acquired a selective advantage over single-celled organisms and increased in population.
Since most single-celled organisms probably came from a lineage where selfishness (the ability to acquire and utilize precious resources to maximize reproductive fitness, at the expense of neighboring cells) was selected for (i.e. survival of the fittest), they had to evolve ways to suppress selfishness, in order to collaborate and function properly within the context of an entire organism. Genes that suppress selfishness are called tumor suppressor genes. Generally, these genes encode proteins that regulate cell cycle, apoptosis (programmed cell death), or are involved in DNA repair. So during the evolution of multi-cellular organisms selection began to work at two levels: the level of the organism, and at the level of individual cells within that organism. Selfishness was shifted from individual cells to the whole multi-cellular organisms.
Considering the evolutionary history of multi-cellular species, cancer is essentially the restoration of selfishness by random mutation and selection at the cellular level. Walking through this step-by-step: loss-of-function mutations arise randomly in tumor suppressor genes2, this causes the cell to grow uncontrollably and selfishly, eventually out-competing neighboring cells for resources (selection), leading to tissue destruction at the detriment of the whole organism.
“All cancers are thought to share a common pathogenesis. Each is the outcome of a process of Darwinian evolution occurring among cell populations within the microenvironments provided by the tissues of a multicellular organism.” 3
The evolution of cancerous cells is a continual process, even after initial tumors develop. Genomic instability—high mutation rates—is a hallmark of cancer, and the more genetically diverse a tumor is, the harder it is to treat. Just as bacterial cells evolve resistance to antibiotics, cancer cells can evolve resistance to anti-cancer treatments like chemotherapy and molecularly targeted therapies. Resistance in both cases is acquired through the same mechanism—natural selection.
Mutation and selection at the cellular level is what creates and sustains cancer. Thus, an understanding of evolutionary principles is fundamental for understanding the development, prevention, and treatment of cancer.
2Ignoring oncogenes here for simplicity. I’m also thinking that during the evolution of multi-cellular organisms oncogenes were just down-regulated to deal with selfishness, as opposed to evolving a new gene as in the case of tumor suppressors. So tumor suppressors are more interesting.