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Antiangiogenic chemotherapeutic agents
1Research Laboratories of Schering AG, Berlin, Germany. michael.schirner@schering.de
Abstract:
The mechanism of action of anticancer chemotherapeutic agents is mainly thought to be due to a direct inhibition of tumor cell proliferation. The enhanced endothelial cell proliferation rate in tumor specimens raised the question whether therapeutic effects of chemotherapeutic agents might be at least partially attributed to an inhibition of tumor angiogenesis. Meanwhile, numerous anticancer chemotherapeutic agents were tested for their antiangiogenic potential. A few agents seem to exert consistent inhibition of tumor angiogenesis even in drug-resistant tumors. Most recent investigations on the antiangiogenic efficacy of different application schedules suggested the use of a tightly spaced, continuous application of appropriate anticancer chemotherapeutic agents. These application schedules are able to exert a strong antiangiogenic effect as indicated by an increase of apoptosis of tumor endothelial cells. Future clinical trials have to determine the therapeutic benefit of novel combination chemotherapy and alternative application schedules.
Insights
Anticancer drugs may inhibit tumor growth by blocking blood vessel formation (angiogenesis). Continuous, tightly spaced drug application shows strong antiangiogenic effects, warranting further clinical trials.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Anticancer chemotherapeutic agents primarily target tumor cell proliferation.
- Increased endothelial cell proliferation in tumors suggests a role for anti-angiogenesis in chemotherapy.
- The antiangiogenic potential of various chemotherapeutic agents has been investigated.
Purpose of the Study:
- To explore the antiangiogenic effects of chemotherapeutic agents.
- To determine if inhibiting tumor angiogenesis contributes to chemotherapy's therapeutic efficacy.
- To evaluate the impact of different drug application schedules on antiangiogenic activity.
Main Methods:
- Testing numerous anticancer chemotherapeutic agents for antiangiogenic potential.
- Investigating the efficacy of different drug application schedules.
- Assessing the antiangiogenic effect by measuring tumor endothelial cell apoptosis.
Main Results:
- Some agents demonstrate consistent inhibition of tumor angiogenesis, even in drug-resistant tumors.
- Tightly spaced, continuous drug application schedules exhibit a strong antiangiogenic effect.
- This enhanced antiangiogenic effect is associated with increased tumor endothelial cell apoptosis.
Conclusions:
- Chemotherapeutic agents may exert therapeutic effects by inhibiting tumor angiogenesis.
- Continuous, tightly spaced drug administration is a promising strategy for antiangiogenesis.
- Further clinical trials are necessary to validate novel combination chemotherapies and application schedules.