Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials

唾液腺癌类器官适用于临床前基因型导向的精准医疗试验

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作者:Tomohiko Ishikawa, Takenori Ogawa, Masahiro Shiihara, Hajime Usubuchi, Yuko Omori, Katsuya Hirose, Taito Itoh, Takuya Yoshida, Ayako Nakanome, Akira Okoshi, Kenjiro Higashi, Ryo Ishii, Masahiro Rokugo, Shun Wakamori, Yasunobu Okamura, Kengo Kinoshita, Yukio Katori, Toru Furukawa

Abstract

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

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