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Updated: May 14, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
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Unlocking the Radiosensitizing Potential of MYC Inhibition in Neuroendocrine Malignancies

Qianyu Guo1, William Yang2, Guy Robinson3

  • 1Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida; Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida; Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida; Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

International Journal of Radiation Oncology, Biology, Physics
|May 12, 2025
PubMed

Insights

MYC oncoproteins drive cancer and therapy resistance. While MYC inhibitors show promise, MYC

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The MYC family of transcription factors (c-MYC, N-MYC, L-MYC) is crucial in oncogenesis and cancer progression.
  • MYC overexpression contributes to therapy resistance, particularly in aggressive neuroendocrine malignancies.
  • Developing MYC inhibitors is challenging due to protein structure, but recent progress is promising.

Purpose of the Study:

  • To review the multifaceted role of MYC overexpression in radiation therapy resistance.
  • To explore MYC's paradoxical effects on radiosensitivity and its role in metastasis.
  • To summarize the development of direct MYC inhibitors as anticancer therapeutics and radiosensitizers.

Main Methods:

  • Literature review of MYC's role in cancer progression, metastasis, and radiation resistance.
  • Analysis of mechanisms by which MYC overexpression influences tumor cell invasion, DNA repair, and immune modulation.
  • Compilation of data on direct MYC inhibitors in preclinical and clinical development.

Main Results:

  • MYC overexpression promotes radiation resistance via increased invasion, enhanced DNA repair, autophagy, and angiogenesis.
  • Conversely, MYC can enhance radiosensitivity by inducing proapoptotic pathways and overwhelming DNA repair.
  • MYC inhibitors are emerging as potential radiosensitizers for various neuroendocrine tumors.

Conclusions:

  • MYC plays a complex role in radiation resistance and metastasis in neuroendocrine malignancies.
  • Direct MYC inhibitors offer a promising therapeutic strategy, potentially as radiosensitizers.
  • Targeting MYC may be beneficial in treating adult and pediatric neuroendocrine tumors, including SCLC and neuroblastoma.

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