Selective and Marked Blockade of Endothelial Sprouting Behavior Using Paclitaxel and Related Pharmacologic Agents

Retinal Toxicity Induced by Chemical Agents

“…There are several case studies reported in the literature linking retinopathies, such as phototoxic maculopathy and cystoid macular edema, induced by paclitaxel and docetaxel [ 141 , 142 , 143 , 144 ], but there are few reports about studies with these compounds in animal models or in vitro models. In C57BL/6J littermate pups, it was seen that paclitaxel treatment was able to reduce the number of retinal vascular branches in a dose-dependent manner during mouse retinal development in vivo [ 145 ]. Another study in a rat model showed that a single intraperitoneal injection of paclitaxel led to an increased retinal vascularity and rosette-like structures in the outer nuclear layer, a lesser number of astrocytes and oligodendrocytes, and some signs of cellular necrosis [ 146 ].…”

Cutaneous angiosarcoma treated with taxane‐based chemoradiotherapy: A multicenter study of 90 Japanese cases

“…Importantly, TLR4 stimulation activated perivascular macrophages to induce endothelial cell‐mediated production of a pro‐metastatic vascular niche during breast cancer colonisation in the lung, 19 suggesting that paclitaxel might be useful for the induction of anti‐tumour immune responses against cancers, but it also induces angiogenesis to promote cancer development. Indeed, paclitaxel interferes with endothelial tip cells promoted by VEGF signalling to suppress their sprouting behaviour, but allow their lumen formation 20 . Notably, a previous clinical trial suggested that the overall response rate of bevacizumab, an anti‐VEGF Ab, was 13%, indicating that VEGF signal blockade is likely insufficient for the treatment of metastatic or locally advanced CAS 21 .…”

“…Indeed, paclitaxel interferes with endothelial tip cells promoted by VEGF signalling to suppress their sprouting behaviour, but allow their lumen formation. 20 Notably, a previous clinical trial suggested that the overall response rate of bevacizumab, an anti‐VEGF Ab, was 13%, indicating that VEGF signal blockade is likely insufficient for the treatment of metastatic or locally advanced CAS. 21 In consideration of these findings from other studies, the different additional effects on the tumour microenvironment between paclitaxel and docetaxel might have impacted OS in each group of the present study.…”

“…Indeed, paclitaxel interferes with endothelial tip cells promoted by VEGF signalling to suppress their sprouting behaviour, but allow their lumen formation. 20 Notably, a previous clinical trial suggested that the overall response rate of bevacizumab, an anti-VEGF Ab, was 13%, indicating…”