Related Experiment Videos
Epidermal growth factor family receptors and inhibitors: radiation response modulators
1Department of Radiation Oncology and UNC/Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Abstract:
Growing evidence suggests that epidermal growth factor family receptors (HERs) play a significant role in radiation response. EGFR expression levels and activation by ligand correlate with radioresistance, and exogenous HER2 expression alters radiation response. Preclinical studies of anti-EGFR anti-HER2 antibodies, and kinase inhibitors that inhibit EGFR, both EGFR and HER2, or all 4 family members show potential for clinical radiosensitization. Early-phase clinical trials of the anti-EGFR antibody, C225, prove the combination of C225 and radiotherapy to be well tolerated and promising. A phase 3 randomized trial in head and neck cancer is underway, and clinical investigation of other HER inhibitors is in progress. The mechanisms(s) of radiation response modulation by HERs appear complex and diverse. Signal transduction initiated by receptor activation promotes survival and proliferation after ionizing radiation, and HER inhibitors affect cellular responses to ionizing radiation (IR) in diverse ways, including inducing apoptosis, cell cycle arrest, and impeding DNA repair. HER signaling and inhibition also affect tumor-stroma interactions, particularly angiogenesis and endothelial survival after IR. Further investigation of the radiation response modulation by EGFR family members and their inhibitors will lead to optimization of this promising therapeutic approach.
Insights
Epidermal growth factor receptors (HERs) significantly impact radiation response. Inhibitors targeting HERs show promise for enhancing radiotherapy effectiveness and patient outcomes in cancer treatment.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Biology
Background:
- Epidermal growth factor receptors (HERs) are increasingly recognized for their role in cancer radiation response.
- EGFR expression and HER2 overexpression are linked to radioresistance.
- Preclinical data suggest HER inhibitors can sensitize tumors to radiation.
Purpose of the Study:
- To review the role of HERs in radiation response.
- To explore the potential of HER inhibitors as radiosensitizers.
- To discuss the mechanisms by which HER signaling affects radiation response.
Main Methods:
- Review of preclinical studies on anti-HER antibodies and kinase inhibitors.
- Analysis of early-phase clinical trials combining HER inhibitors with radiotherapy.
- Examination of proposed mechanisms of HER-mediated radiation response modulation.
Main Results:
- Anti-EGFR and anti-HER2 antibodies, along with various kinase inhibitors, demonstrate potential for radiosensitization.
- Early clinical trials with the anti-EGFR antibody C225 show a well-tolerated and promising combination with radiotherapy.
- Ongoing Phase 3 trials and further investigations are evaluating other HER inhibitors.
Conclusions:
- HER signaling pathways are complex modulators of cellular and tumor responses to ionizing radiation.
- HER inhibitors can induce apoptosis, cell cycle arrest, and impair DNA repair, thereby enhancing radiation effects.
- Targeting HERs may optimize radiotherapy by influencing tumor-stroma interactions, including angiogenesis and endothelial cell survival.