Novel antiangiogenic drugs for the management of breast cancer: new approaches for an old issue?

Abstract

Since angiogenesis plays an important role in cancer growth, infiltration and metastasis, many agents targeting this pathway have been developed over the last decade. Antiangiogenic drugs interfere with this process and may inhibit neoplastic growth or induce tumor dormancy by blocking the expanding network of newly formed capillaries. Despite the initial promise, targeting angiogenesis in breast cancer has not reached major breakthroughs. Nevertheless, the immunologic role of VEGF deserves to be further explored. We aim to describe the biological mechanisms which underlie the role of angiogenesis in breast cancer carcinogenesis, to depict its contribution to the metastatic process and to review the most important clinical trials testing angiogenic inhibitors in breast cancer, including monoclonal antibodies and novel small molecules.

Keywords:

• antiangiogenic drugs
• breast cancer
• monoclonal antibodies
• tyrosine kinases inhibitors
• VEGF
• VEGFR

Financial & competing interests disclosure

G Aprile received grants from Roche, Sanofi and Eli-Lilly as speaker meetings focused on gastrointestinal cancers. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Angiogenesis is one of the hallmarks of tumor growth, invasion and metastases and its inhibition is a therapeutic option for the treatment of cancer.

• Bevacizumab is the most studied antiangiogenic drug in breast cancer.

• The role of bevacizumab in the therapeutic management of breast cancer is controversial.

• In the advanced setting, the addition of bevacizumab to chemotherapy regimens obtained a modest but significant improvement in progression-free survival with manageable toxicity but no overall survival advantage.

• Clinical trials testing other antibodies targeting angiogenesis, such as aflibercept or ramucirumab, produced disappointing results.

• Tyrosine kinases inhibitors have some activity, but their toxicities limit the possibility of combination with chemotherapy.

• Overall survival and biomarker data are critical to understand how to apply these data to the clinic.

• Future challenges of antiangiogenic therapy include a better understatement of the underpinning disease-specific biology.