The history and future perspectives of anti-angiogenics

Abstract

Angiogenesis is the process of formation of new blood vessels from existing ones and it is involved in both physiological and pathological conditions. In 1971, Dr. Folkman hypothesized that for tumour development, an angiogenic “switch” is activated, where the balance between pro-and anti-angiogenic regulators is tipped in favor of the first and induces neovascularization in the tumour. Tumour-associated angiogenesis is crucial for tumour growth, progression, and metastasis. For these reasons, the last decades there has been significant progress in the development of anti-angiogenic strategies. However, these strategies showcase severe limitations in both pre-clinical and clinical setting. Biological differences in anatomy and therapy response between the animal models and the human in clinical trials, low treatment efficiency, development of severe side effects, anti-angiogenic resistance and relapse post-treatment are but a few challenges that current therapies need to overcome. For that reason, development and application of novel approaches is required to improve anti-angiogenic therapy. Combination therapy constitutes the main way to overcome the limitations of conventional treatment. Application of chemotherapy or immunotherapy with administration of anti-angiogenic inhibitors demonstrated positive results with improved therapy efficiency. In this review, an overview of anti-angiogenic therapy is presented, analyzing the applications and limitations of anti-angiogenics and the developed novel strategies.