Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

Abstract

Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.

The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies

“…In the recent past, drug screens have also been reported for PDOs established from many other organs, including liver [40], ovarian [32] and stomach [33] tumours. In addition to drug screens, a recent study of head and neck tumours applied radiation screens in PDOs and compared the results with the clinical outcome [34]. Three patients relapsed after radiotherapy within one to six months, consistent with the finding that their organoid lines were classified as most resistant.…”

“…While these experiments are important to characterize in greater detail the interplay between tumour and immune cells, it needs to be shown to what degree they will add to the predictive value of organoids in clinical set-ups. First trial experiments using organoids for radiation and drug screens showed good correlation with the respective in vivo patient responses [33,34].…”

Cysteamine-bicalutamide combination treatment restores alpha-ketoglutarate and corrects proximal tubule phenotype in cystinosis

“…For tubuloid experiments, the drug safety screening was performed using a protocol derived from Driehuis et al 64 . In short, BME was dissolved by incubation in 1 mg/mL dispase II for 30 min at 37…”

Intestinal ex vivo organoid culture reveals altered programmed crypt stem cells in patients with celiac disease

“…Because the organoids possess many functional and structural characteristics of the original tissue and retain their tumorigenic potential, this technology has now opened completely new perspectives in human research. Organoids generated from individual patients offer the future to study and identify molecular mechanisms in pathophysiology, in transformation and progression of tumor growth, screening and prediction of response and sensitivity to chemotherapeutic drugs, and ultimately the possibility of personalized therapy 6,7 .…”