Researchers have uncovered a cellular mechanism that helps explain why some ovarian tumours become resistant to platinum chemotherapy. The study, published in Cell Reports and led in part by Sachi Horibata at Michigan State University College of Human Medicine, shows that cisplatin — long known for causing DNA damage — also disrupts microtubules, the internal scaffold that helps cells keep their shape and survive stress. Cancer cells can reprogram the so-called "tubulin code," a set of structural changes that stabilise microtubules and help cells withstand treatment.
Central to this adaptation is tubulin polymerization promoting protein 3 (TPPP3). The team found that higher TPPP3 levels enable cancer cells to stabilise microtubules and resist the effects of cisplatin or carboplatin. Clinical data in the study showed that patients with lower TPPP3 expression lived longer and had better responses to therapy. In laboratory models, removing TPPP3 significantly restored tumour cell sensitivity to cisplatin, supporting a direct role for the protein in resistance.
Following these results, researchers plan to develop drugs that target TPPP3 and to test whether the protein can serve as a biomarker to identify patients at risk of resistance. Future work will examine how this mechanism affects current chemotherapy combinations and whether it operates in other cancer types. The findings may also help investigators better understand common chemotherapy side effects, such as nerve damage, hair loss and hearing loss.
The research involved contributors from Michigan State University and several NIH centres, and it received funding from MSU, the Japan Society for the Promotion of Science and intramural programs at the National Institutes of Health, among others.
Difficult words
- mechanism — a process that produces a particular result
- microtubule — a tiny structural tube inside cellsmicrotubules
- tubulin — a protein that builds microtubule structures
- stabilise — make something more steady or firm
- resistance — ability to withstand a harmful effect
- biomarker — a measurable sign used to indicate disease
- polymerization — process of molecules linking into long chains
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could a drug that targets TPPP3 change treatment for ovarian cancer patients?
- What are possible advantages and risks of using TPPP3 as a biomarker?
- In what way might the disruption of microtubules by cisplatin explain common chemotherapy side effects?
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