Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modelling and Radiation Dose Optimization

Description: Summary from the GEO: "Background: Effective radiation treatment (RT) for recurrent nasopharyngeal cancers (NPC), featuring an intrinsic hypoxic sub-volume, remains a clinical challenge. Lack of disease‐specific in-vitro models, together with difficulties in establishing patient derived xenograft (PDX) models, have further hindered development of personalized therapeutic options. Methods: Here in, we established two NPC organoid lines from recurrent NPC PDX models and further characterized and compared these models with original patient tumors using RNA sequencing analysis. Organoids were cultured in hypoxic conditions to examine the effects of hypoxia and radioresistance. These models were then utilized to determine the radiobiological parameters, such as α/β ratio and oxygen enhancement ratio (OER), characteristic to radiosensitive normoxic and radioresistant hypoxic NPC, using simple dose-survival data analytic tools. The results were further validated in-vitro and in-vivo, to determine the optimal boost dose and fractionation regimen required to achieve effective NPC tumor regression. Results: Despite the differences in tumor microenvironment due to the lack of human stroma, RNA sequencing analysis revealed good correlation of NPC PDX and organoid models with patient tumors. Additionally, the established models also mimicked inter-tumoral heterogeneity. Hypoxic NPC organoids were highly radioresistant and had high α/β ratio compared to its normoxic counterparts. In-vitro and in-vivo fractionation studies showed that hypoxic NPC was less sensitive to RT fractionation scheme and required a large bolus dose or 1.4 times of the fractionated dose that was effective against normoxic cells in order to compensate for oxygen deficiency. Conclusion: This study is the first direct experimental evidence to predict optimal RT boost dose required to cause sufficient damage to recurrent hypoxic NPC tumor cells, which can be further used to develop dose-painting algorithms in clinical practice."

Overall design from the GEO: "RNA sequencing data of 8 NPC patient tumors, 2 PDXs lines 296T and 250T and corresponding organoid lines from the 2 PDXs"

Subject of Study

Homo sapiens

Subject(s)

Nasopharyngeal Neoplasms

Organoids

OncoTree Cancer Type(s)

Nasopharyngeal Carcinoma

Access via GEO
Plain Text Data of expression profiling by high throughput sequencing and Non-coding RNA profiling by high throughput sequencing
Accession #: GSE164544

Access via SRA
RNA Sequence reads for 67 samples
Accession #: SRP301225

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA691161
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications: Lucky SS, Law M, Lui MH, et al. Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization. Front Oncol. 2021;11:622244. Published 2021 Feb 23.
Data Type: Genomic
Equipment Used: Illumina NovaSeq 6000
Software Used: SRA Toolkit
The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.
Dataset Format(s): Plain Text, SRA, TAR, XLSX
Data Tool(s): RNA Seq
Dataset Size: 71.8 Mb (XLSX), 60.9 Mb (TAR of TXT), 296.7 Gb (SRA)

Data Catalog Record Updated: 2023-12-07