Angiogenesis and Chromene-based Antiangiogenic Therapeutic Agents
Pp. 151-188 (38)
Olivia Pontes, Ana Raquel-Cunha, Sofia Oliveira-Pinto, Fatima Baltazar, Olga Martinho and Marta Costa
Tumor vascularization plays an essential role in cancer progression. Tumor
vasculature provides oxygen and nutrients to cancer cells and removes waste products
which is important for the rapid growth of tumors. Importantly, the tumor associated
vessels are also used for tumor cell metastization, in which cancer cells invade distant
organs. Therefore, inhibition of angiogenesis constitutes one of the elected targeted
approaches for cancer treatment.
The first FDA approved antiangiogenic drug was bevacizumab, an antibody against
vascular endothelial growth factor (VEGF) that has been used to treat metastatic
tumors. However, despite the initial increase in survival rates, no major benefit in
global survival was described and patients ended up relapsing due to acquired
resistance. Further, monotherapy with this type of agents is not generally associated
with improvement of survival, being antiangiogenic therapy a strategy that is worth
pursuing as combination therapy. Thus, the efficacy of angiogenesis inhibitors is still a
Several families of naturally occurring compounds have been described as
antiangiogenic agents with promising results, such as stilbenes, chalcones, terpenoids,
phenylethanoids and others. Due to their remarkable structure variety, plant
polyphenols have been extensively studied and found to inhibit angiogenesis and
metastasis through the regulation of multiple signaling pathways involved in cancer
development. Chromenes and coumarins, such as crolibulin (EPC2407), have already
been identified as vascular disrupting agents with promising antiangiogenic properties.
The substitution pattern highly influences the activity and mode of action in various
types of cancer. Specifically, chromenes are found to regulate the expression of VEGF,
matrix metalloproteinases (MMPs) and receptor tyrosine kinases RTKs (e.g. EGFR)
This chapter focuses on the antiangiogenic properties of chromenes, coumarins and
derivatives, highlighting the recent progress in drug development and clinical
Angiogenesis, Antiangiogenic agents, Cancer, Chromenes.
Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, Braga, Portugal.