Breast tumour angiogenesis

Stephen B Fox,Adrian L Harris,Daniele G Generali

doi:10.1186/bcr1796

Abstract

The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized.

Highlights

It has been 3 years since the last critical review of antiangiogenic therapy was published in Breast Cancer Research [1], and since the central importance of tumour neovascularization has been emphasized by clinical trials in various tumour types, including breast cancer
The critical contribution of this angiogenic factor in controlling many of the processes involved in angiogenesis and its importance as a paradigm for the rational design of an anticancer agent have been among the successes of antiangiogenic treatment, which was first suggested by Judah Folkman more than 35 years ago
The attractiveness of the antiangiogenic approach has always been the wide therapeutic window, since all tumours are angiogenesis dependent, that angiogenesis is highly restricted in the adult, that endothelium of the vessels are accessible and that any treatment would be amplified through subsequent tumour infarction

Summary

Introduction

It has been 3 years since the last critical review of antiangiogenic therapy was published in Breast Cancer Research [1], and since the central importance of tumour neovascularization has been emphasized by clinical trials in various tumour types, including breast cancer. In vitro bevacizumab inhibits VEGF-induced endothelial cell proliferation and migration, and in xenograft models of a range of tumour types (including breast cancer) tumour growth is significantly decreased by bevacizumab [95,96]. Novel use of conventional chemotherapy as antiangiogenic agents It is likely that over the few years the designer agents discussed above will be supplemented by conventional chemotherapeutic agents, including cyclophosphamide, paclitaxel, doxorubicin and vincristine, which appear to have antitumour effects through interfering with new vessel formation when used at ‘metronomic’ doses This is where chemotherapy is administered frequently at low doses, which avoids myelosuppression and other dose-limiting side effects and which would otherwise require rest periods, but this approach inhibits tumour growth indirectly by damaging endothelial cells. Inhibiting γ-secretase function would prevent Notch signal transduction; γ-secretase inhibitors have been developed that perform this function

Conclusion

Miller KD

Findings

Folkman J