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Live Imaging to Quantify Cellular Radiosensitivity in Patient-Derived Tumor Organoids
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Published on: April 5, 2024

Radiotherapy-induced signal transduction.

Adly Yacoub1, Anna Miller, Ruben W Caron

  • 1Department of Biochemistry, Virginia Commonwealth University, 401 College Street, Richmond, Virginia 23298, USA.

Endocrine-Related Cancer
|January 30, 2007
PubMed
Summary

Tumor cells adapt to radiation by activating survival pathways like ERBB and ERK1/2. Inhibiting these pathways can protect or sensitize cancer cells to radiation, depending on exposure duration.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Ionizing radiation triggers compensatory intracellular survival pathways in tumor cells.
  • Radiation exposure initially inhibits protein tyrosine phosphatase and activates ERBB receptors and downstream signaling.

Purpose of the Study:

  • To investigate the dynamic adaptation of tumor cells to ionizing radiation.
  • To explore the role of ERBB receptor and extracellular regulated kinase (ERK)1/2 signaling in tumor cell survival and radiosensitivity.

Main Methods:

  • Utilized human carcinoma cell lines and isogenic HCT116 cells.
  • Applied small-molecule inhibitors to block ERBB receptor phosphorylation and ERK1/2 pathway activity.
  • Analyzed changes in ERBB receptor and ligand expression, and activation of ERK1/2 and AKT signaling.

Main Results:

  • Radiation-induced ERK1/2 activation promoted paracrine ligand release, re-activating ERBB signaling.
  • Short-term inhibition (3 h) of ERBB/ERK1/2 protected cells from radiation; prolonged inhibition (48-72 h) enhanced radiosensitivity.
  • RAS family activation and p53 mutational status modulated ERBB receptor/ligand expression and downstream signaling, impacting radiosensitivity.

Conclusions:

  • Tumor cells dynamically adapt to therapeutic challenges like radiation and genetic alterations to maintain viability.
  • Targeting ERBB receptor and ERK1/2 pathways offers potential strategies for modulating radiosensitivity.
  • Understanding these adaptive mechanisms is crucial for optimizing cancer radiotherapy.