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Updated: Feb 17, 2026

Using Primary Neurosphere Cultures to Study Primary Cilia
Published on: April 14, 2017
Losers of Primary Cilia Gain the Benefit of Survival
Gladiola Goranci-Buzhala1, Elke Gabriel1, Aruljothi Mariappan1
1Center for Molecular Medicine Cologne and Institute of Biochemistry I of the University of Cologne, Cologne, Germany.
Abstract:
In this issue, Zhao and colleagues demonstrate that loss of primary cilia in medulloblastoma cells confers resistance to the Smoothened (SMO) inhibitor sonidegib. When treated with sonidegib, medulloblastoma cells lost their cilia and gained resistance. Surprisingly, loss of cilia is associated with recurrent mutations in ciliogenesis genes that are eventually able to drive drug resistance. These findings uncover a previously unknown mechanism of cancer cells in gaining a "persister-like" state against anticancer agents at the expense of losing primary cilia. Cancer Discov; 7(12); 1374-5. ©2017 AACRSee related article by Zhao et al., p. 1436.
Insights
Medulloblastoma cells develop drug resistance by losing primary cilia when treated with the Smoothened (SMO) inhibitor sonidegib. This cilia loss, linked to mutations, creates a drug-resistant "persister-like" state.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Medulloblastoma is a common pediatric brain tumor.
- The Smoothened (SMO) signaling pathway is a therapeutic target in medulloblastoma.
- Primary cilia play roles in various cellular processes, including development and signaling.
Purpose of the Study:
- To investigate the role of primary cilia in medulloblastoma response to SMO inhibitors.
- To identify mechanisms of drug resistance in medulloblastoma.
Main Methods:
- Treatment of medulloblastoma cells with the SMO inhibitor sonidegib.
- Analysis of primary cilia status and gene mutations in drug-resistant cells.
- Assessment of drug resistance mechanisms.
Main Results:
- Loss of primary cilia in medulloblastoma cells confers resistance to sonidegib.
- Medulloblastoma cells lose primary cilia upon sonidegib treatment, leading to acquired resistance.
- Cilia loss is associated with recurrent mutations in ciliogenesis genes, driving drug resistance.
Conclusions:
- Primary cilia loss is a novel mechanism for medulloblastoma cells to acquire a "persister-like" state against SMO inhibitors.
- Targeting ciliogenesis or restoring cilia function may overcome drug resistance in medulloblastoma.
- Understanding this mechanism opens new avenues for medulloblastoma treatment strategies.
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