1. Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids
- Author
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Yoshiyuki Tsukamoto, Shusaku Kurogi, Tomotaka Shibata, Kosuke Suzuki, Yuka Hirashita, Shoichi Fumoto, Shinji Yano, Kazuyoshi Yanagihara, Chisato Nakada, Fumi Mieno, Keisuke Kinoshita, Takafumi Fuchino, Kazuhiro Mizukami, Yoshitake Ueda, Tsuyoshi Etoh, Tomohisa Uchida, Toshikatsu Hanada, Mutsuhiro Takekawa, Tsutomu Daa, Kuniaki Shirao, Shuichi Hironaka, Kazunari Murakami, Masafumi Inomata, Naoki Hijiya, and Masatsugu Moriyama
- Subjects
Organoids ,Neoplasms ,Humans ,Antineoplastic Agents ,Cell Biology ,Docetaxel ,Cisplatin ,Phosphorylation ,Molecular Biology ,Biomarkers ,Pathology and Forensic Medicine - Abstract
Despite recent advances in sequencing technology and large-scale drug screenings employing hundreds of cell lines, the predictive accuracy of mutation-based biomarkers is still insufficient as a guide for cancer therapy. Therefore, novel types of diagnostic methods using alternative biomarkers would be highly desirable. We have hypothesized that sensitivity-specific changes in the phosphorylation of signaling molecules could be useful in this respect. Here, with the aim of developing a method for predicting the response of cancers to cisplatin using a combination of specific biomarker(s) and patient-derived tumor organoids (PDOs), we found that cisplatin-sensitive cell lines or PDOs showed enhanced phosphorylation of c-Jun (p-c-Jun) within 24 h after cisplatin treatment. We also compared the responses of 6 PDOs to cisplatin with the therapeutic effect of neoadjuvant chemotherapy (docetaxel/cisplatin/5-fluorouracil) in 6 matched patients. Mechanistically, the c-Jun induction was partly related to TNF signaling induced by cisplatin. Our data suggest that enhanced phosphorylation of c-Jun in response to cisplatin treatment could be a predictive biomarker for the efficacy of cisplatin in selected cancer patients.
- Published
- 2021