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Creating Matched In vivo/In vitro Patient-Derived Model Pairs of PDX and PDX-Derived Organoids for Cancer Pharmacology Research
Published on: May 5, 2021
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Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization
Sasidharan Swarnalatha Lucky1, Martin Law2, Ming Hong Lui3
1Institute of Bioengineering and Nanotechnology, Agency for Science Technology and Research (ASTAR), Singapore, Singapore.
Frontiers in Oncology
|March 18, 2021
Summary
Developing new nasopharyngeal cancer (NPC) models revealed hypoxic NPC is radioresistant. This finding guides optimal radiation boost doses for recurrent tumors, improving treatment effectiveness.
Area of Science:
- Oncology
- Radiation Oncology
- Cancer Biology
Background:
- Recurrent nasopharyngeal cancer (NPC) poses challenges for effective radiation treatment (RT) due to intrinsic hypoxia.
- Limited availability of disease-specific in vitro and patient-derived xenograft (PDX) models hinders personalized therapeutic development for NPC.
Purpose of the Study:
- To establish and characterize NPC organoid models from recurrent NPC PDX models.
- To investigate the impact of hypoxia on radioresistance in NPC models.
- To determine radiobiological parameters and optimize RT strategies for hypoxic recurrent NPC.
Main Methods:
- Established two NPC organoid lines from recurrent NPC PDX models.
- Utilized RNA sequencing to compare organoids with original patient tumors.
- Cultured organoids under hypoxic conditions to assess radioresistance.
- Determined radiobiological parameters (α/β ratio, OER) using dose-survival data.
- Validated findings through in vitro and in vivo fractionation studies.
Main Results:
- NPC organoid models showed good correlation with patient tumors and mimicked inter-tumoral heterogeneity.
- Hypoxic NPC organoids exhibited significant radioresistance and a higher α/β ratio compared to normoxic counterparts.
- Hypoxic NPC demonstrated reduced sensitivity to standard RT fractionation, requiring higher doses for effective tumor regression.
Conclusions:
- Established NPC organoid models provide valuable tools for studying radioresistance and developing personalized RT.
- Hypoxic NPC requires adjusted RT fractionation or higher boost doses to overcome oxygen deficiency and achieve tumor control.
- This research offers direct experimental evidence for predicting optimal RT boost doses for recurrent hypoxic NPC, aiding clinical dose-painting algorithm development.
