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, characterized by immunohistochemistry and DNA sequencing and a biobank was established. In addition to organoids of the most common HNC tumor type 'squamous cell carcinoma', the biobank also contains organoids of rare tumour types such as salivary gland tumors or intestinal-type adenocarcinoma.
The organoids were exposed to chemotherapy, radiotherapy, and a series of targeted agents. The response of the organoids was compared 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. The radiosensitizing potential of cisplatin and carboplatin was reproduced in the organoids. As in clinical studies, cetuximab showed heterogeneous results and induced radioprotection in most models. Targeted HNC treatments were tested, indicating potential new treatment options that may allow stratification of treatment in the future. In preclinical studies, PIK3CA mutations were identified as biomarkers for response to alpelisib. In clinical trials, however, a more heterogeneous response to treatment with alpelisib was observed. Even organoids with PIK3CA mutations in this study could not predict a response to alpelisib.
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
