As a cancer researcher, I often wonder about patients after their ordeal with cancer. How does the body change after facing a life-threatening illness? Do cells in our body hold the memory of disease in some way? Survivorship is a word that describes life after a traumatic event, a life in which many aspects of health, from the psychosocial to the physical, are changed. In this blog post, I hope to delve into the cellular level of survivorship and explore how surviving cancer and cancer therapy can alter our biology fundamentally.
All cells in our body contain DNA, which is an instruction manual for day-to-day duties that the cell must perform to sustain life. DNA is what we inherit from our ancestors, our parents, and what we pass on to our children. Therefore, the cells in our body are very careful about keeping DNA intact and unchanged through a biological process called “fidelity.” Interestingly, most cancer patients carry permanent changes to their DNA after treatment. One striking example is to think of patients that receive bone marrow transplants. These patients will always have two different types of DNA in their bodies: their own DNA and their donor’s! In other examples, the patient’s own DNA has minor or major alterations, changing the writing of the instruction manual, which in turn can affect how the manual is read and interpreted.
If you were to take a look at many different cancer survivors, even long after they have stopped cancer therapy and have been cancer-free, DNA from various different parts of their body would show low levels of damage. What does damage mean? If you think about a china vase, and if you were to drop it so that it didn’t shatter, but merely cracked on the surface, that would be the closest metaphor for what’s happening here. If you consider the china vase to be the DNA, you can imagine that the DNA is damaged but not completely deteriorated. How does this damage occur? During the course of cancer therapy, patients are exposed to drugs or radiation that directly damage DNA. Most of the time, the cancer cells are the ones impacted; however, normal cells can also be affected. The major consequence of damage is accelerated aging in most survivors. Their tissues and cells look as though they are from an individual much older than they are.
Prolonged levels of stress and damage to the DNA from cancer treatment can change the way a cell reads its DNA. Epigenetics is the study of how DNA is read and interpreted in the cell and epigenetic marks on the DNA help the cell figure out which parts of the DNA to read. In cancer patients, epigenetic marks are globally changed over the course of therapy and remarkably these changes remain long after exposure to chemotherapy is stopped. Patients with cancer have more epigenetic marks signifying “do not read” being added to the DNA. In normal individuals, an increase in these marks has been associated with routine aging., In cancer patients, irrespective of chronological age, these marks can be present post therapy, signifying profound molecular aging. What remains to be investigated is whether these marks and their subsequent accumulation in survivors is a direct result of toxicity of therapy or a by-product of DNA damage leading to changes in epigenetics.
With roughly 15.5 million cancer survivors currently alive in the US alone, it becomes absolutely critical to understand the biology of survivorship. The science of survivorship helps us understand the biological burden of going through cancer therapy and, in turn, this valuable knowledge allows us to develop less burdensome therapies as a result. From a physical and now a molecular standpoint as well, survivorship is a monumental feat of resilience that comes with an unwanted side-effect: aging.
Peer edited by Denise St. Jean and Eliza Thulson.
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