Cancer arises when cells acquire genetic mutations that cause them to grow unabated. Cancer development usually requires that multiple mutations occur within a given cell, with each mutation bestowing an additional layer of fitness that allows the cancer to invade tissues, evade the immune system and outgrow normal cells.
This process requires time, but it can be accelerated by environmental exposures or inherited syndromes that make cancer causing mutations more likely to occur. Many known cancer risk factors – such as advanced age, smoking and chronic inflammation – disproportionately affect adults rather than children. This raises a critical question that shapes our field and our patients’ lives:
Why do children get cancer?
To answer this question, we need to understand some important differences between childhood and adult cancers.
Children get different kinds of cancer than adults.
Childhood cancers usually arise from cells that are in the process of developing rather than cells that are in the process of aging. This may accelerate cancer formation because embryonic cells are primed to grow extensively.
Childhood cancers are caused by different mutations than adult cancers.
Childhood cancers typically carry fewer (but more potent) mutations than adult cancers, so less time and fewer genetic mistakes are required for a cell to become cancerous.
Genetic programs that regulate normal childhood development might also enable cancer initiation.
In other words, imagine that a given mutation requires support from normal, childhood-specific genes in order to cause cancer. The mutation is only dangerous if it occurs at a specific age. Outside that context, the mutation does not cause cancer. In this model, childhood cancer formation reflects an abnormal extension of normal developmental biology, in contrast to adult cancer formation.
Many pediatric cancer patients may have some degree of inherited cancer predisposition.
In other words, cancers can evolve earlier in life because cells have some degree of predisposition. Note that these predispositions often do not align with formally diagnosed syndromes.
Altogether, these differences illustrate how childhood cancers are not simply early-arising versions of adult cancers. If we are going to improve childhood cancer treatment, we must first understand why children get specific cancers. How do childhood-specific mutations cause cancer? How does normal childhood development shape the biology of pediatric cancers?