Endoglin-based biological therapy in the treatment of angiogenesis-dependent pathologies

ABSTRACT

Introduction: Alterations in the process of angiogenesis, either by excess or by defect, are present in different common pathologies. For this reason, great efforts are being made toward the development of pro- and anti-angiogenic therapies. Since endoglin levels are enhanced in tissues undergoing angiogenesis, and changes in its expression lead to alterations in vessel formation, endoglin has become an ideal target for these types of therapies.

Areas covered: In this review, the role of endoglin in angiogenesis is summarized. In addition, the authors review pro- and anti-angiogenic therapies that are currently being used and new approaches that target endoglin. The article includes therapies that are both in preclinical and clinical development.

Expert opinion: Endoglin is a very good target for anti-angiogenic therapy, as demonstrated by the positive results obtained with anti-endoglin antibodies. However, although endoglin in pro-angiogenic therapies has been successful in vitro, its use has not yet reached clinical settings. Moreover, the authors believe that establishing the exact role of endoglin in angiogenesis is essential and that this should be the next step in this field in the coming years.

KEYWORDS:

• Angiogenesis
• anti-angiogenic therapy
• endoglin
• endothelium
• proangiogenic therapy

Article highlights

• Endoglin plays a major role in regulating angiogenesis. Active angiogenesis is associated with endoglin overexpression, whereas defective endoglin expression leads to impaired angiogenesis. Further research on the precise role of endoglin in every process and phase of angiogenesis is needed.

• Monoclonal antibodies against endoglin have been shown to be effective therapeutic agents against pathologies associated with endoglin overexpression, such as tumor growth and wet age-related macular degeneration, alone or in association with other antiangiogenic therapies (VEGF pathway inhibitors) in preclinical models of these diseases.

• Ongoing humanized anti-endoglin antibody-based clinical trials have confirmed their efficacy in treating tumor growth and wet age-related macular degeneration, and there are fewer side effects when using this therapy.

• The use of endoglin as a target for pro-angiogenic therapy, although feasible, has scarcely been studied and none of these results has been translated to the clinical setting.

• The antiangiogenic properties of sEng make it a good candidate for antiangiogenic therapy but further research is required.

This box summarizes key points contained in the article.

Acknowledgements

This manuscript has had professional language editing by Emma-Jane Keck from the Language Centre of the University of Salamanca.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The studies carried out by the authors have been supported by grants from the Ministerio de Economía y Competitividad of Spain (grant no.’s SAF2010-15881 and SAF2013-45784-R), the Junta de Castilla y Leon (Grant No. GR100), the Fundación Renal Iñigo Alvarez de Toledo, the Kidney Research Network REDINREN (Grants RD06/0016/0013, RD12/0021/0032 and RD016/0009/0025)) and the Instituto de Salud Carlos III, via grant PI16/00460 and co‐funded by FEDER. Furthermore, C Ollauri-Ibáñez is supported by a fellowship from the Ministerio de Economía y Competitividad of Spain.