When a cancerous tumor takes hold in a patient, the cure can seem worse than the disease. Patients suffer nausea, hair loss and suppressed immunity following radiation or chemotherapy because a naturally occurring protein called p53 has been activated in response to the DNA damage caused by the treatments. If p53 detects DNA damage or tumor growth and tries to shut down the runaway growth, it can trigger the deaths of many noncancerous cells.
A new discovery by researchers here suggests a way to help the tumor-suppressing protein distinguish between healthy cells and cancerous cells.
It seems that p53 leaps into aggressive action in any cell with DNA damage, regardless of whether or not the cell has started runaway growth. By disabling one part of the p53 protein called TAD1, the team created a version of p53 with a more nuanced reaction. It tolerates cells that have DNA damage but haven't begun to grow into a tumor.
Laura Attardi, PhD, senior author of the study, explained in a press release why this could help reduce the side effects of radiation and chemotherapy:
"Separating these responses may allow the identification of ways to inhibit the detrimental effects of radiotherapy and chemotherapy - both of which damage DNA -without putting a patient at risk for developing new tumors."
The release provides more details that helped me understand why the discovery could lead to more tolerable tumor-shrinking treatments:
If the two distinct activities of p53 in healthy cells can be decoupled - say, by a drug impairing TAD1's function but sparing TAD2's - it might be possible to avoid the massive healthy-cell die-off responsible for nausea, hair loss, immune deficiency and nerve damage that usually occur during radiotherapy or chemotherapy, without promoting new tumor development. Disabling p53's TAD1 region would allow cells that have sustained DNA damage in the course of these therapies to live to another day, but TAD2's still-intact tumor-suppressor function in those otherwise normal cells would guard against those cells becoming cancer cells.
Previously: Facing the hard reality of cancer treatment