Researchers report that MGMT methylation and MGMT protein expression follow circadian cycles, so tumour repair capacity changes during the day. Because MGMT repairs the DNA damage that temozolomide (TMZ) causes, these daily rhythms alter how sensitive glioblastoma tumours are to chemotherapy.
The team analysed five years of patient biopsy data provided by WashU Medicine colleagues Joshua Rubin, Will Leidig, and Omar Butt and observed an increased likelihood that morning biopsies were scored as methylated. Herzog argued that biopsy timing could therefore affect diagnostic classification and suggested a chronodiagnostic approach to refine treatment decisions.
Graduate student Maria Gonzalez-Aponte measured MGMT levels in tumour cells and patient GBM samples, while math biologist Olivia Walch helped build a mathematical model. The model notes that TMZ needs several hours to cause DNA damage and trigger cell death, so dosing shortly after an MGMT protein peak gives a longer window when tumour repair is slower. Walch also warned that finding the right dosing time may depend on dose and individual circadian differences.
- Next steps: clinical tests of chronotherapy with TMZ.
- Study timing of other signals that affect GBM growth.
- Investigate drugs like dexamethasone to avoid harmful times.
The work received support from the National Institutes of Health and NCI, and from Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine. Source: Washington University in St. Louis.
Difficult words
- methylation — Addition of chemical tags to DNA.
- expression — Process where a gene makes its protein.
- circadian — A natural daily rhythm in living organisms.
- biopsy — A sample taken from tissue for testing.biopsies
- chronodiagnostic — Using time of day to improve diagnosis.
- chemotherapy — Treatment that uses drugs to kill cancer.
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could timing diagnostic biopsies change treatment decisions for patients? Give reasons based on the article.
- What practical challenges might doctors face when testing chronotherapy in clinical settings? Suggest possible solutions.
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