Classical VEGF, Notch and Ang signalling in cancer angiogenesis, alternative approaches and future directions (Review)
- Nunzia Caporarello
- Gabriella Lupo
- Melania Olivieri
- Martina Cristaldi
- Maria Teresa Cambria
- Mario Salmeri
- Carmelina Daniela Anfuso
Published online on: August 7, 2017
Copyright: © Caporarello et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
Angiogenesis is the formation of new vessels starting from pre-existing vasculature. Tumour environment is characterized by ‘aberrant angiogenesis’, whose main features are tortuous and permeable blood vessels, heterogeneous both in their structure and in efficiency of perfusion and very different from normal vessels. Therapeutic strategies targeting the three pathways chiefly involved in tumour angiogenesis, VEGF, Notch and Ang signalling, have been identified to block the vascular supply to the tumour. However, phenomena of toxicity, development of primary and secondary resistance and hypoxia significantly blunted the effects of anti-angiogenic drugs in several tumour types. Thus, different strategies aimed to overcome these problems are imperative. The focus of the present review was some principal ‘alternative’ approaches to classic antiangiogenic therapies, including the cyclooxygenase-2 (COX-2) blockade, the use of oligonucleotide complementary to the miRNA to compete with the mRNA target (antimiRs) and the inhibition of matrix metalloproteinases (MMPs). The role of blood soluble VEGFA as a predictive biomarker during antiangiogenic therapy in gastric, ovarian and colorectal cancer was also examined.