July 12, 2019
For those undergoing chemotherapy, the side effects can be serious. Chemotherapy drugs like cisplatin, kill cells by damaging DNA in replicating cells. This is excellent when the cells are cancerous and replicating often, but problematic when those cells are normal cells that replicate less frequently like skin, bone marrow etc.
University of North Carolina School of Medicine researchers set out to discover the pattern of DNA repair in healthy cells, with a view to discover the best time to administer cisplatin to patients. Successful treatment requires hitting cancer cells with chemotherapy drugs that cause DNA damage when they are least capable of repairing the damage, but the healthy cells are most able to.
In healthy mouse cells they saw that DNA repair was under the control of the body’s circadian clock. Most tumor cells however do not have a functional clock. The researchers discovered that the sections of DNA that were under the influence of the clock (known as transcribed DNA) were mostly repaired within 48 hours. However, other sections of DNA not transcribed under the influence of the clock, took much longer to repair after being damaged by cisplatin. This slower repair isn’t a problem in non-replicating healthy cells, but it is in cancer cells. The slow DNA repair can lead to cell death in the rapidly replicating cancer cells because the DNA damage caused by cisplatin persists and interferes with the ability of these cells to keep replicating.
Additional studies will be required before human trials, but if successful, this research could lead to modifications in treatment plans that would simultaneously exploit this weakness in cancer cells and minimize damage in normal cells. Specifically, in chronochemotherapy treatments which are designed to maximize tumor damage and minimize side effects by optimizing drug delivery times.
Source: Science Daily
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