Journal
LIFE SCIENCES
Volume 252, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.117670
Keywords
Sprouting; Intussusceptive angiogenesis; Tumor; Biomarkers; Angiogenic switch
Funding
- Department of Science and Technology, INPSIRE Faculty Program, Government of India [DST/INSPIRE/04/2017/002913]
- Science and Engineering Research Board (SERB), India [SRG/2019/000337]
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Deregulation of angiogenesis is a key reason for tumor growth and progression. Several anti-angiogenic drugs in clinical practice attempt to normalize abnormal tumor vasculature. Unfortunately, these drugs are ineffective due to the development of resistance in patients after drug holidays. A sizable literature suggests that resistance to these anti-angiogenic drugs occurs due to various compensatory mechanisms of tumor angiogenesis. Therefore, we describe different compensatory mechanisms of tumor angiogenesis, and explain why intussusceptive angiogenesis (IA), is a crucial mechanism of compensatory angiogenesis in tumors which resist anti-VEGF (vascular endothelial growth factor) therapies. IA is often overlooked due to the scarcity of experimental models. Therefore, we examine data from existing experimental models and our novel ex-ovo model of angiogenesis in chick embryos, and explain the important genes and signaling pathways driving IA. Using bioinformatic analyses of major genes regulating conventional sprouting angiogenesis (SA) and intussusceptive angiogenesis, we provide fresh insights on the `angiogenic switch' which regulates the transition from SA to IA. Finally, we examine the interplay between molecules regulating SA, IA, and molecules known to promote tumor progression. Based on these analyses, we conclude that intussusceptive angiogenesis (IA) is a promising therapeutic target for developing effective anti-cancer treatment regimes.
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