Inhibitory Effect of PRMT5/MTA Inhibitor on MTAP‐Deficient Glioma May Be Influenced by Surrounding Normal Cells
2024

Impact of Normal Cells on Glioma Treatment with PRMT5/MTA Inhibitor

Sample size: 180 publication Evidence: moderate

Author Information

Author(s): Wang Yunjie, Sun Xiaohui, Ma Runchen, Zhang Xiaofan, Ji Shengmin, Liu Zhaofeng, Yang Gangqiang, Wang Hongbo, Zhang Peng, Zhang Jianzhao, Tian Jingwei

Primary Institution: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong

Hypothesis

The effectiveness of PRMT5/MTA inhibitors on MTAP-deficient gliomas may be influenced by the presence of surrounding normal cells.

Conclusion

The presence of normal cells significantly reduces the effectiveness of the PRMT5/MTA inhibitor MRTX1719 on MTAP-deficient gliomas.

Supporting Evidence

  • MTAP-deficient gliomas were surrounded by a large number of MTAP-expressing normal cells.
  • The presence of these cells significantly reduced the inhibitory effect of MRTX1719 on glioma cells.
  • MRTX1719 showed a significantly lower IC50 in MTAP-deficient glioma cells compared to normal cells.
  • MTAP deletion is common in glioma, occurring in approximately 50% of cases.

Takeaway

This study shows that normal cells around brain tumors can make cancer treatments less effective.

Methodology

The study used in vitro and in vivo models to analyze the effects of MRTX1719 on MTAP-deficient gliomas coexisting with normal cells.

Limitations

The study's findings may not fully translate to clinical settings due to the complexity of tumor environments.

Participant Demographics

180 patients with glioma (112 males and 68 females, aged from 2 to 80 years)

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1002/cam4.70526

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