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Oral Cancer Organoids Uncover Insights into Chemotherapy Resistance
- Researchers from the Institute of Science Tokyo are investigating minimal residual disease (MRD) in tongue cancer through a library of tongue cancer organoids (TCOs).
- The organoids, 3D tissue cultures that replicate the architecture and functionality of their originating tissues, accurately represent the biology of tongue cancer better than cell lines.
- The study involved collecting surgical tissue from 28 untreated tongue cancer patients to create a comprehensive library of organoids characterising different tumour states.
- The team compared the responses of chemo-resistant TCOs to cancer drug cisplatin and discovered the cells adopt a state akin to embryonic diapause, which allows them to suspend cellular activities temporarily, making them resistant to chemotherapy agents.
- Further analyses found that the activation of autophagy in addition to cholesterol biosynthesis pathways sustain the survival of chemo-resistant cancer cells.
- Inhibitors against these pathways converted the chemo-resistant state of the organoids to a chemo-sensitive state.
- The research shows how personalising medicine through the analysis of organoids can predict how individual tumours may respond to treatment, aiding clinicians in tailoring treatment regimens to improve outcomes.
- The research once again underscores the importance of differentiating between the underlying biology of different tumour states, which is crucial for developing personalised medical treatments.
- This method of TCO library construction holds promise for discovering actionable drug targets and biomarkers essential for personalised medicine in oral cancers.
- The insights gained through this groundbreaking work offer newfound hope to patients fighting oral cancer and will reshape therapeutic landscapes in oncology.
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