miRNA biomarkers may help personalize glioblastoma care

A German study has found that overexpression of specific micro(mi)RNAs in native tumour tissue and primary glioblastoma (GBM) cell cultures are positively correlated with increased effectiveness of tumour-treating fields (TTFields) treatment, pointing to the potential of miRNAs as biomarkers in predicting treatment response to TTFields.

The single-centre exploratory study assessed cell viability of primary GBM cell cultures before and after 72 hours of TTFields treatment, which was applied in vitro to the cultures. Correlation analyses of treatment effects on the primary GBM cultures, and expression levels of miR­NAs-21, -26a, -34a, -181c, -181d, and -485-5p in these cells and in corresponding native tumour tissue, untreated primary GBM cell cultures, and plasma samples were then carried out. The cell cultures were prepared from GBM tumour tissue obtained from 21 GBM patients (female, 9; male, 12) during tumour resection. The six miRNAs were chosen due to observations from previous studies that their presence was associated with higher sensitivity to TTFields or alkylating chemotherapy in GBM patients, as well as their known roles in cell‑cycle regulation and oncogenic pathways affected by TTFields’ mechanism of action. Reference blood samples from 10 healthy donors were also analyzed. [Brain Tumour Pathol 2026;doi:10.1007/s10014-025-00527-x]

Response rates of primary GBM cell cultures to TTFields treatment ranged between 0.63 and 78.26 percent, with a mean rela­tive reduction of cell viability of 48.53 percent. Expression of miRNA-26a in tumour tissue (p=0.041) and miRNAs-21, -26a, and -181c in untreated control cultures (p<0.05) positively correlated with an increased relative reduction of cell viability, indicating increased sensitivity to TTFields. However, positive correlation between TTFields sensitivity and the other miRNAs was not found in this small study sample.  

GBM remains one of the most challenging central nervous system cancers to treat, with gross total resection, radiotherapy and systemic chemotherapy delivering only modest survival improvements. TTFields, which disrupt tumour cell mitosis using alternating electric fields, thus inducing autophagy and promoting DNA damage, have become an important adjunct of treatment in selected patients with GBM, but clinical responses vary widely. [Neuro Oncol 2021;23:1231-1251; J Am Med Assoc 2017;318:2306-2316; Radiat Oncol 2017;12:1-13; Sci Rep 2015;5:1-16; Front Oncol 2021;11:1-12; Neurooncol Adv 2022;4:1-10]

“Predicting effectiveness of TTFields prior to their application could improve cost efficiency for healthcare systems and support patients’ decision to undergo treatment despite potential physical or mental hardship that the treatment would entail,” the authors opined.

Given the exploratory nature of this study with focus on primary cell cultures, the authors noted that further experiments with knockdown or overexpression of the miRNAS in established GBM cell cultures are needed to corroborate their findings and establish basic causality. Clinical stud­ies are also warranted to explore if the effectiveness of TTFields can be predicted by treatment response of primary GBM cell cultures and to corroborate epigenetic findings with the clinical course of GBM patients treated with TTFields.