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

doi:10.1016/j.isci.2023.106695

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

iScience. 2023 Apr 20;26(5):106695. doi: 10.1016/j.isci.2023.106695. eCollection 2023 May 19.

Authors

Tomohiko Ishikawa^{1

2}, Takenori Ogawa³, Masahiro Shiihara², Hajime Usubuchi⁴, Yuko Omori², Katsuya Hirose², Taito Itoh², Takuya Yoshida^{1

2}, Ayako Nakanome¹, Akira Okoshi¹, Kenjiro Higashi¹, Ryo Ishii¹, Masahiro Rokugo¹, Shun Wakamori¹, Yasunobu Okamura^{5

6}, Kengo Kinoshita^{5

6

7}, Yukio Katori¹, Toru Furukawa²

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
² Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
³ Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
⁴ Department of Pathology, Sendai Kousei Hospital, Sendai 980-0873, Japan.
⁵ Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine, Sendai 980-8573, Japan.
⁶ Tohoku University Tohoku Medical Megabank Organization, Sendai 980-8573, Japan.
⁷ Tohoku University Graduate School of Information Sciences, Sendai 980-8579, Japan.

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.

Keywords: Cancer; Cell biology; Health sciences; Stem cells research.