CDC42-effector interaction inhibitors alter patterns of vessel arborization in skin and tumors <i>in vivo</i>.

ABSTRACT: 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 to

SUBMITTER: Vuong LM 

PROVIDER: S-EPMC12432855 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature