01982nas a2200313   4500000000100000008004100001260001500042653001400057653002100071653002900092653001400121653002200135653002900157653004400186100001600230700001400246700001600260700001600276700001900292700001800311700001800329700002100347700001900368700002000387245012700407856007200534520104800606022001401654       2024                            d  c2024-11-0510aautophagy10achemo-resistance10acholesterol biosynthesis10acisplatin10aembryonic diapose10aminimal residual disease10apatient-derived tongue cancer organoids1 aMiwako Sase1 aTaku Sato1 aHajime Sato1 aFuyuki Miya1 aShicheng Zhang1 aHiroshi Haeno1 aMihoko Kajita1 aTadahide Noguchi1 aYoshiyuki Mori1 aToshiaki Ohteki00aComparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease  uhttps://www.sciencedirect.com/science/article/pii/S15345807240060753 aThe 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.  a1534-5807