High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations

Area of Science:

• Oncology
• Radiation Oncology
• Drug Discovery

Background:

• Proton beam therapy (PBT) is a key treatment for head and neck squamous cell carcinoma (HNSCC).
• Optimizing PBT efficacy through drug combinations requires effective screening methods.
• Limited data exists on drug combinations enhancing PBT for HNSCC.

Purpose of the Study:

• To evaluate a 3D tumor spheroid screening platform for assessing cellular sensitivity to PBT.
• To investigate drug combinations with PBT for HNSCC treatment.
• To identify synergistic effects between PBT and targeted drugs.

Main Methods:

• Utilized a 3D tumor spheroid model with HNSCC cell lines (Fadu and Cal27) on a 384-pillar/well plate.
• Exposed spheroids to varying doses of proton irradiation and targeted drugs (olaparib, adavosertib).
• Assessed cell viability using Calcein staining and calculated combination indices for drug synergy.

Main Results:

• The 3D spheroid platform provided quantitative, dose-dependent cell viability data for PBT and drugs.
• Cal27 spheroids demonstrated greater synergy with olaparib combined with PBT compared to Fadu spheroids.
• Adavosertib did not show synergistic effects with PBT in either HNSCC cell line.

Conclusions:

• The 3D pillar/well array platform is effective for rapid, quantitative screening of PBT and drug combination sensitivity.
• Combining PBT with olaparib presents a potentially effective treatment strategy for HNSCC.
• Further research into PBT and olaparib combinations is warranted for HNSCC patients.