New research shows MGMT gene methylation and protein levels rise and fall across the day. MGMT repairs DNA damage caused by the chemotherapy drug temozolomide (TMZ), so these daily rhythms can change tumor sensitivity to treatment.
Researchers analysed five years of biopsy data from WashU Medicine colleagues Joshua Rubin, Will Leidig, and Omar Butt and found morning biopsies were more likely to be scored as methylated. Herzog suggested that biopsy timing could influence diagnosis and proposed a chronodiagnostic approach to improve treatment choice.
Graduate student Maria Gonzalez-Aponte measured MGMT levels in tumor cells and patient samples. Olivia Walch built a mathematical model that predicts when TMZ would be most effective. The team plans clinical tests of chronotherapy and will study drugs like dexamethasone to avoid treatment times that might promote tumor growth. The work was supported by NIH, NCI, Siteman Cancer Center, Barnes-Jewish Hospital, and WashU Medicine.
Difficult words
- methylation — a chemical change to DNA affecting gene activity
- biopsy — removal of tissue to check for diseasebiopsies
- chronotherapy — treatment timed to the body's daily cycles
- temozolomide — a chemotherapy drug used to treat some tumors
- model — a simple representation to predict outcomes
- sensitivity — how easily something responds to a treatment
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Discussion questions
- How could the time of day affect medical tests or treatment in your experience?
- What are possible advantages or problems of giving cancer treatment at certain times of day?
- If doctors used a chronodiagnostic approach, how might that change patient appointments in a hospital?
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