Organoids of head and neck tumors for treatment optimization and biomarker identification
2023
Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, Netherlands
In this study, organoids were prepared from tumor tissues of HNC patients (head neck cancer, tumors of the head and neck region, including squamous cell carcinomas and salivary gland adenocarcinomas) and characterized by immunohistochemistry and DNA sequencing. An HNC biobank of 110 models, including 65 tumor models, was established.
The organoids were exposed to chemotherapy, radiotherapy, and a series of targeted agents. The response of the organoids was correlated with the clinical response of the patients. CRISPR-Cas9-based gene editing of organoids was used to validate biomarkers.
Organoids exhibited the DNA alterations found in HNC. A comparison between organoids and patient response to radiotherapy showed that treatment options could be better managed in the adjuvant setting. In organoids, the radiosensitizing potential of cisplatin and carboplatin was validated. However, cetuximab produced radioprotection in most models. Targeted HNC treatments were tested in 31 models, indicating potential new treatment options that may allow stratification of treatment in the future. Activating PIK3CA mutations did not predict response to alpelisib in organoids. Inhibitors of protein arginine methyltransferase 5 (PRMT5) were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC.
Organoids have the potential to serve as a diagnostic tool in personalized medicine for HNC. The response of organoids to radiotherapy (RT) in vitro showed a trend mimicking clinical response, indicating the predictive potential of patient-derived organoids. In addition, organoids could be used for biomarker discovery and validation.
Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification
Else Driehuis, Rosemary Millen, Hans Clevers
Added on: 06-30-2023
[1] https://www.cell.com/med/fulltext/S2666-6340(23)00135-6?_returnURL=https%3a%2f%2flinkinghub.elsevier.com%2fretrieve%2fpii%2fS2666634023001356%3fshowall%3dtrue&emci=63e63142-3b09-ee11-907c-00224832eb73&emdi=05abcfa6-350a-ee11-907c-00224832eb73&ceid=2015591
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