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Combined Radiochemotherapy: Metalloproteinases Revisited
Verena Waller1, Martin Pruschy1
1Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Frontiers in Oncology
|May 31, 2021
Summary
Ionizing radiation triggers cellular stress responses and signaling. Metalloproteinase inhibitors targeting the tumor microenvironment may enhance radiotherapy efficacy by overcoming resistance mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ionizing radiation induces DNA damage and complex stress responses in tumor cells.
- These responses involve intra- and intercellular signaling, influencing tumor radioresistance.
- Metalloproteinases are key regulators of cell communication and matrix remodeling in the tumor microenvironment.
Purpose of the Study:
- To review the role of metalloproteinases in the irradiated tumor microenvironment.
- To discuss the therapeutic potential of metalloproteinase inhibitors combined with radiotherapy.
Main Methods:
- Literature review on metalloproteinases and radiotherapy.
- Analysis of metalloproteinase function in tumor signaling and resistance.
- Discussion of targeted metalloproteinase inhibition strategies.
Main Results:
- Metalloproteinases regulate tumor growth, angiogenesis, immune infiltration, and dissemination.
- Dysregulation of metalloproteinases contributes to radioresistance.
- Previous broad-spectrum inhibitors showed toxicity; specific inhibitors are promising.
Conclusions:
- Metalloproteinases are crucial in the irradiated tumor microenvironment.
- Targeting metalloproteinases, especially with specific inhibitors, offers a viable strategy to enhance radiotherapy outcomes.
- Combination therapy with specific metalloproteinase inhibitors and radiotherapy warrants further investigation.
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