@article{4986,
  keywords = {autophagy, chemo-resistance, cholesterol biosynthesis, cisplatin, embryonic diapose, minimal residual disease, patient-derived tongue cancer organoids},
  author = {Miwako Sase and Taku Sato and Hajime Sato and Fuyuki Miya and Shicheng Zhang and Hiroshi Haeno and Mihoko Kajita and Tadahide Noguchi and Yoshiyuki Mori and Toshiaki Ohteki},
  title = {Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease},
  abstract = {The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both in vitro and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed “heritable” embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC.},
  year = {2024},
  journal = {Developmental Cell},
  month = {2024-11-05},
  issn = {1534-5807},
  url = {https://www.sciencedirect.com/science/article/pii/S1534580724006075},
  doi = {10.1016/j.devcel.2024.10.007},
}