Twenty percent of children treated with drugs called anthracyclines suffer heart failure later in life seemingly because the chemotherapy changes the function of cells that normally repair heart injury.
It is a truth that clinical trials on chemotherapy drugs are never conducted with the under 12s. Doctors and oncologists routinely claim that they know best, with their experience. Their job is to save the child from cancer.
Although pediatric oncologists give lower doses of anthracycline chemotherapy than when the drugs were introduced more than 40 years ago to reduce the immediate risk of death, little is understood about complications later in life.
It would now seem that cardiac fibroblasts which act as a sort of caretaker cell in the heart and other tissues of the body are damaged by chemotherapy agents. Dr. Aune, a pediatric oncologist in the Joe R. and Teresa Lozano Long School of Medicine, who led the study, believes these effects could be long-term.
In many cases of cancer the p53 gene is damaged. This normally controls regular cell division and acts as a tumour-suppressor gene. It also seems to protect healthy cells like the cardiac fibroblasts from damage. When it, itself, is damaged it seems to expose the cardiac fibroblasts to the chemo drugs.
In experiments on mice lacking a p53 gene, exposure to chemo causes altered fibroblast function. This stops their ability to migrate to repair tissues in heart injury. Indeed, cardiac fibroblasts treated with anthracycline show less migration.
"The overarching hypothesis we have in the lab is that damage to this cell population, the cardiac fibroblast, isn't innocuous" Dr. Aune said. "These cells can have their properties changed by exposure to gene-damaging agents. And then theoretically over time, that may be one contributor to the late effects that we see."
Researchers believe that poor fibroblast function might then produce an inability to respond to other conditions such as high blood pressure or heart attacks.
Chris Woollams, former Oxford University Biochemist added, “At CANCERactive we have covered child chemo and not just increased heart attack risks but suicide risk several times before”.
Go to: Child chemo and heart attack and suicide risk
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Reference
- T. R. Mancilla, L. R. Davis, G. J. Aune. Doxorubicin-induced p53 interferes with mitophagy in cardiac fibroblasts. PLOS ONE, 2020; 15 (9): e0238856 DOI: 10.1371/journal.pone.0238856