In this study, Snoek and colleagues aimed to enhance the effectiveness of thermoradiotherapy by investigating the potential of microRNAs (miRNAs) as treatment sensitizers. MiRNAs are small, non-coding RNAs that play a central role in gene regulation and have been shown to target key components of the DNA damage response in cancer. Using a high-throughput 3D tumor spheroid screening platform, the team tested hundreds of miRNAs in cervical cancer cells and validated promising candidates across additional cervical and head and neck cancer models.
They identified 18 miRNAs that significantly enhanced the effects of thermoradiotherapy, six of which — miR-16, miR-27a, miR-181c, miR-221, miR-224, and miR-1293 — showed inhibition of key DNA repair proteins (ATM, DNA-PKcs, Ku70/80, and RAD51). Some of these miRNAs also demonstrated a link with treatment outcomes in patient samples, making them promising predictive biomarkers for therapy response.
This research lays the groundwork for the development of miRNA-based sensitizers, that could be used to boost the effects of thermoradiotherapy, particularly for patients unable to receive chemotherapy. It also paves the way for more personalized cancer treatment, as certain miRNA expression patterns may help predict who will benefit most.
Find the full publication here: High-throughput 3D spheroid screens identify microRNA sensitizers for improved thermoradiotherapy in locally advanced cancers
Involved researchers
- Dr. Barbara Snoek (LEXOR/Radiation Oncology)
- Dr. MengFei Xu (Pathology)
- Prof.dr. Renske Steenbergen (Pathology)
- Dr. Arlene Oei (LEXOR/Radiation Oncology)
- Prof.dr. Mark van de Wiel (Epidemiology and Data Science)
- Prof.dr. Lukas Stalpers (Radiation Oncology)
- Dr. Angelina Huseinovic (Pathology)
- Prof.dr. Victor van Beusechem (Medical Oncology)
Funding
This research was supported by Stichting Cancer Center Amsterdam (CCA2019-9-59) and the China Scholarship Council Grant (202008420215).