Cilia at the Crossroads of Tumor Treating Fields and Chemotherapy

Dev Neurosci. 2023;45(3):139-146. doi: 10.1159/000529193. Epub 2023 Jan 17.


Glioblastoma (GBM), the most common and lethal primary brain tumor in adults, requires multi-treatment intervention which unfortunately barely shifts the needle in overall survival. The treatment options after diagnosis and surgical resection (if possible) include irradiation, temozolomide (TMZ) chemotherapy, and now tumor treating fields (TTFields). TTFields are electric fields delivered locoregionally to the head/tumor via a wearable medical device (Optune®). Overall, the concomitant treatment of TTFields and TMZ target tumor cells but spare normal cell types in the brain. Here, we examine whether primary cilia, microtubule-based "antennas" found on both normal brain cells and GBM cells, play specific roles in sensitizing tumor cells to treatment. We discuss evidence supporting GBM cilia being exploited by tumor cells to promote their growth and treatment resistance. We review how primary cilia on normal brain and GBM cells are affected by GBM treatments as monotherapy or concomitant modalities. We also focus on latest findings indicating a differential regulation of GBM ciliogenesis by TTFields and TMZ. Future studies await arrival of intracranial TTFields models to determine if GBM cilia carry a prognostic capacity.

Keywords: Glioma; Neural development; Primary cilia; TTFields; Temozolomide.

Publication types

  • Review

MeSH terms

  • Adult
  • Brain*
  • Cilia*
  • Humans
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use


  • Temozolomide

Grants and funding

M.R.S. is supported by a 2022 American Association for Cancer Research (AACR)-Novocure Tumor-Treating Fields Research (Grant No. #22-60-62-SARK). L.P.D. is supported by the NIH (R21NS116578 and 1R01NS121075) and the Florida Department of Health (22L06).