Is it useful to think of cancer as a stem cell disease, a condition that (largely) arises because stem cells become dysfunctional? The evidence seems to suggest that at least some cancers arise from somatic cells taking on stem cell properties, while a body of work indicates that at least some cancerous tissues are supported by small populations of cancer stem cells that might be targeted for destruction. Here researchers are interested in the bigger picture, the nature of the relationship between stem cell function, stem cell resilience, cancer, and aging. In an era that will soon enough seen the widespread use of regenerative medicine and rejuvenation therapies that, by their nature, will increase stem cell function in older people, it is perhaps worth thinking about how cancer risk fits into all of this.
A stem-cell theory of cancer predicates that not only does the cell affect the niche, the niche also affects the cell. It implicates that even though genetic makeup may be supreme, cellular context is key. When we attempt to solve the mystery of a long cancer-free life, perhaps we need to search no further than the genetics and epigenetics of the naked mole-rat. When we try to unlock the secrets in the longevity and quality of life, perhaps we need to look no further than the lifestyle and habits of the super centenarians. We speculate that people with Down's syndrome and progeria age faster but have fewer cancers, because they are depleted of stem cells, and, as a consequence, have fewer opportunities for stem cell defects that could predispose them to the development of cancer. We contemplate whether these incredible experiments of nature may provide irrefutable evidence that cancer is a stem-cell disease-fewer aberrant stem cells, fewer cancers; no defective stem cells, no cancer.
A stem-cell theory of aging and cancer reiterates a fundamental oncological principle: although genetic makeup may be pivotal, cellular context is paramount. When the genome and epigenome that regulate aging and malignancy are also stemness genes and stem-like properties, they reaffirm the key role that stem-cell quality and quantity play in longevity and cancer. We suspect that long-lived, cancer-spared mammals maintain a youthful genome and epigenome because they are equipped with a larger and healthier pool of stem cells. We contemplate that people with Down's syndrome and progeria age faster but have fewer cancers because they are depleted of stem cells and therefore have fewer opportunities for stem-cell defects that render one prone to cancer formation.
Therefore, the benefit of longevity needs to be balanced against the risk of malignancy. Intuitively, how we manage to conserve stemness and delay senescence is key.