Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials
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
Affiliations
Tomohiko Ishikawa
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Takenori Ogawa
Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Masahiro Shiihara
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Hajime Usubuchi
Department of Pathology, Sendai Kousei Hospital, Sendai 980-0873, Japan
Yuko Omori
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Katsuya Hirose
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Taito Itoh
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Takuya Yoshida
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Ayako Nakanome
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Akira Okoshi
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Kenjiro Higashi
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Ryo Ishii
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Masahiro Rokugo
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Shun Wakamori
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Yasunobu Okamura
Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine, Sendai 980-8573, Japan; Tohoku University Tohoku Medical Megabank Organization, Sendai 980-8573, Japan
Kengo Kinoshita
Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine, Sendai 980-8573, Japan; Tohoku University Tohoku Medical Megabank Organization, Sendai 980-8573, Japan; Tohoku University Graduate School of Information Sciences, Sendai 980-8579, Japan
Yukio Katori
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Toru Furukawa
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Corresponding author
Summary: 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.
