2025-07-14 カリフォルニア大学アーバイン校(UCI)
<関連情報>
- https://news.uci.edu/2025/07/14/uc-irvine-researchers-develop-promising-drugs-to-halt-tumor-skin-disease-blood-vessel-growth/
- https://www.cell.com/iscience/fulltext/S2589-0042(25)01232-5
CDC42-エフェクター相互作用阻害剤がin vivoにおける皮膚と腫瘍の血管新生パターンを変化させる CDC42-effector interaction inhibitors alter patterns of vessel arborization in skin and tumors in vivo
Linh M. Vuong ∙ Stephanie Hachey ∙ Jessica Shiu ∙ … ∙ Christopher C.W. Hughes ∙ Marco De Vivo ∙ Anand K. Ganesan
iScience Published:July 14, 2025
DOI:https://doi.org/10.1016/j.isci.2025.112971
Graphical abstract
Highlights
- Optical clearing and 3D tracing can quantify vessel arborization in skin and tumors
- RhoJ plays a selective role in controlling vessel arborization in skin in vivo
- CDC42 interaction inhibitors block vessel arborization within melanoma tumors
- CDC42 inhibitors that target RhoJ can inhibit skin vessel arborization in vivo
Summary
Skin tumors require a vascular supply to grow beyond 1 mm in depth, yet existing anti-angiogenesis agents are largely ineffective at treating melanoma tumors arising in skin. Using an approach that integrates antibody infusion, optical tissue clearing, multiphoton imaging, and vessel tracing, we identified the CDC42 GTPase RhoJ as a critical regulator of skin vessel arborization. Small molecules that target both RhoJ and CDC42 (CDC42 interaction inhibitors), but not those that target only CDC42 (CASIN), inhibit vessel branching in mouse skin in vivo and vascular organoids in vitro. This anti-vascular effect was not limited to skin, as CDC42 interaction inhibitors blocked melanoma tumor vascularization and inhibited tumor growth to a similar degree as Braf inhibitors. Taken together, this work identifies small molecules that target RhoJ as selective tumor anti-vascular agents. RhoJ-targeting drugs have a particular proclivity for blocking skin vascularization, nominating them as new treatments for inflammatory/vascular skin disease.
