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Related Experiment Video

Updated: Jun 13, 2026

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
12:55

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Published on: February 16, 2015

Radiosensitization of Glioblastoma by the K-ras Inhibitor RMC-6236.

Hong Shik Yun1, Tamalee R Kramp1, Mary Sproull1

  • 1Radiation Oncology Branch, National Cancer Institute, 10 Center Drive, Building 10, Bethesda, MD, 20892, USA.

Biorxiv : the Preprint Server for Biology
|June 12, 2026
PubMed
Summary

Inhibiting KRAS/RAS signaling with RMC-6236 enhances glioblastoma cell radiosensitivity by increasing DNA damage and mitotic catastrophe. This combination therapy shows promise for improving glioblastoma treatment outcomes.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Glioblastoma (GBM) exhibits poor prognosis and resistance to radiotherapy.
  • Current radiosensitizing strategies for GBM are limited.
  • KRAS/RAS signaling is a potential target for overcoming radioresistance.

Purpose of the Study:

  • To investigate if KRAS/RAS signaling inhibition can enhance radiation response in GBM.
  • To evaluate the radiosensitizing potential of RMC-6236, an RAS(ON) inhibitor.

Main Methods:

  • GBM cell lines were treated with radiation and KRAS inhibition (siRNA or RMC-6236).
  • Assessed radiation-induced KRAS/MAPK activation, radiosensitivity (clonogenic assay), DNA damage (γH2AX), cell cycle, and mitotic catastrophe.
  • Evaluated in vivo efficacy in an orthotopic GBM xenograft model.

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Last Updated: Jun 13, 2026

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Main Results:

  • Radiation induced transient KRAS/MAPK activation in GBM cells.
  • KRAS inhibition (siKRAS or RMC-6236) enhanced radiosensitivity across all cell lines.
  • RMC-6236 increased radiosensitivity (enhancement factors 1.33-1.46) by promoting persistent DNA damage and mitotic catastrophe.
  • Combination therapy in vivo significantly prolonged survival.

Conclusions:

  • Radiation-induced KRAS signaling mediates GBM radioresistance.
  • Inhibiting KRAS/RAS signaling with RMC-6236 enhances GBM radiation response in vitro and in vivo.
  • RMC-6236 is a potential radiosensitizer for GBM, warranting clinical trials.