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Angiogenesis research: guidelines for translation to clinical application
J Folkman1, T Browder, J Palmblad
1Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. judah.folkman@tch.Harvard.edu
Abstract:
Angiogenesis research is being translated to the clinic. Certain guidelines may facilitate this effort. Recruitment of endothelial cells by a tumor is an early event in angiogenesis, a process regulated at genetic and epigenetic levels. The microvascular endothelial cell has become an important second target in cancer therapy. Angiogenesis inhibitors are either "direct" or "indirect" and their optimal dosing depends on a different logic than conventional chemotherapy. Conversely, antiangiogenic scheduling of chemotherapy can by-pass drug resistance. Like all solid tumors, hematologic malignancies are angiogenesis-dependent. Further, angiogenesis is modulated by proteins and cells from the hematopoietic and hemostatic systems. Clinical testing of angiogenesis inhibitors has accentuated the need for surrogate markers of tumor angiogenesis activity. Microvessel density, so valuable as a prognostic indicator of metastatic risk, cannot determine efficacy of an angiogenesis inhibitor. In the future, angiogenesis inhibitors may be added to chemotherapy or to radiotherapy, or to other modalities. Also, combinations of angiogenesis inhibitors may be administered together.
Insights
Translating angiogenesis research into clinical practice requires specific guidelines. Understanding tumor endothelial cell recruitment and the role of angiogenesis inhibitors is key for effective cancer therapy.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Therapeutics
Background:
- Tumor angiogenesis, the recruitment of endothelial cells, is a critical process in cancer progression.
- Microvascular endothelial cells are increasingly targeted in cancer therapy.
- Angiogenesis is fundamental to both solid tumors and hematologic malignancies.
Purpose of the Study:
- To review the translation of angiogenesis research into clinical applications.
- To discuss the mechanisms and targeting of tumor angiogenesis.
- To highlight the evolving role of angiogenesis inhibitors in cancer treatment.
Main Methods:
- Review of current literature on angiogenesis research and clinical translation.
- Analysis of direct and indirect angiogenesis inhibitors.
- Discussion of antiangiogenic scheduling and combination therapies.
Main Results:
- Angiogenesis inhibitors require distinct dosing strategies compared to conventional chemotherapy.
- Antiangiogenic scheduling can overcome chemotherapy resistance.
- Hematologic malignancies are also dependent on angiogenesis.
Conclusions:
- Effective clinical translation of angiogenesis research necessitates clear guidelines.
- New surrogate markers are needed to assess angiogenesis inhibitor efficacy.
- Future cancer treatment paradigms will likely involve combinations of angiogenesis inhibitors with chemotherapy, radiotherapy, or other modalities.