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Combined effects of angiostatin and ionizing radiation in antitumour therapy
H J Mauceri1, N N Hanna, M A Beckett
1Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637, USA.
Abstract:
Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumour progression. Angiostatin, a proteolytic fragment of plasminogen that was first isolated from the serum and urine of tumour-bearing mice, inhibits angiogenesis and thereby growth of primary and metastatic tumours. Radiotherapy is important in the treatment of many human cancers, but is often unsuccessful because of tumour cell radiation resistance. Here we combine radiation with angiostatin to target tumour vasculature that is genetically stable and therefore less likely to develop resistance. The results show an antitumour interaction between ionizing radiation and angiostatin for four distinct tumour types, at doses of radiation that are used in radiotherapy. The combination produced no increase in toxicity towards normal tissue. In vitro studies show that radiation and angiostatin have combined cytotoxic effects on endothelial cells, but not tumour cells. In vivo studies show that these agents, in combination, target the tumour vasculature. Our results provide support for combining ionizing radiation with angiostatin to improve tumour eradication without increasing deleterious effects.
Insights
Combining radiation therapy with angiostatin, an angiogenesis inhibitor, effectively targets tumor vasculature and enhances tumor eradication. This combination therapy shows reduced tumor growth with no increased toxicity to normal tissues.
Area of Science:
- Oncology
- Vascular Biology
- Radiation Oncology
Background:
- Angiogenesis is crucial for tumor progression and metastasis.
- Radiotherapy is a key cancer treatment but faces challenges due to tumor cell radiation resistance.
- Angiostatin, a plasminogen fragment, inhibits angiogenesis and tumor growth.
Purpose of the Study:
- To investigate the combined effects of ionizing radiation and angiostatin on tumor growth and vasculature.
- To assess the potential of this combination therapy to overcome radiation resistance and improve cancer treatment outcomes.
- To evaluate the toxicity profile of the combined treatment on normal tissues.
Main Methods:
- Combination of ionizing radiation with angiostatin in preclinical cancer models.
- In vitro studies on endothelial cells and tumor cells to assess cytotoxic effects.
- In vivo studies in four distinct tumor types to evaluate anti-tumor efficacy and toxicity.
Main Results:
- Demonstrated an anti-tumor interaction between ionizing radiation and angiostatin across four tumor types.
- Observed combined cytotoxic effects on endothelial cells in vitro, but not on tumor cells.
- Showed that the combination therapy targets tumor vasculature in vivo without increasing toxicity to normal tissues.
Conclusions:
- Combining ionizing radiation with angiostatin offers a promising strategy for enhancing tumor eradication.
- This combination therapy targets tumor vasculature, a genetically stable component, potentially reducing resistance.
- The approach shows potential for improving cancer treatment efficacy without significant adverse effects on normal tissues.