Together, these data suggest that the Cdc42 C81Y mutation disrupts canonical Cdc42 signalling while promoting context-dependent cellular and inflammatory responses. This study provides mechanistic insight into how Cdc42 C81Y may contribute to PID-associated malignancy and underscores its role at the intersection of cytoskeletal regulation and immune dysregulation.

We also examine the latest advances in leveraging CDC42's structural features for selective inhibition, analyzing the mode of action and chemical structures of current inhibitors. These insights aim to inform the design of improved molecules with broad therapeutic potential.

In vivo studies with immunocompromised mice bearing HER2-BM tumors demonstrated that M6 inhibits tumor growth and metastasis to the lungs, livers, and kidneys by ~90%, comparable to MBQ-167. These findings suggest that M6 exhibits potent anticancer properties both in vitro and in vivo, potentially contributing to the sustained efficacy of MBQ-167 in metastatic breast cancer.

P2, N=17, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2027 --> Apr 2032

P=N/A, N=180, Not yet recruiting, Ningbo Medical Centre Lihuili Hospital; Ningbo Medical Centre Lihuili Hospital

This study demonstrates that RES significantly inhibits the proliferation, invasion, and migration of PC cells by mediating the succinylation of CDC42, which in turn inhibits the CDC42 signaling pathway and disrupts the dynamics of the ECM. This mechanism highlights the potential of RES as an anticancer agent and provides new insights for the development of therapeutic strategies for PC.

P2, N=17, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2029 --> Nov 2027

Further proteomic and bioinformatics analysis implied that LIUS + MBs may reduce Cdc42 activity by upregulating the expression of GTPase-activating proteins (GAPs). Our research provides novel insight into the mechanism by which LIUS + MBs can inhibit tumor metastasis, highlighting its role in disturbing the Cdc42-mediated cytoskeletal remodelling of filopodia.

The serum CDC42 level associates with LNM, visceral metastasis, and worse prognosis in mCRPC patients underwent abiraterone plus prednisone therapy. However, future prospective, large-scale, and controlled studies are needed for validation.

Tetrandrine suppressed CM cell growth by triggering G0/G1 cell cycle arrest via IL-6/CDC42 inhibition. Tetrandrine should be a promising compound for CM treatment.

In conclusion, our results indicate a new mechanism whereby UBE2T-mediated ubiquitination positively controls the UBE2T/CDC42/CD276 axis to upregulate tumor cell expression of CD276 and thereby impair CD8+ T cells function, ultimately leading to tumor cell immune escape and BrM.

P2, N=17, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2031 --> Feb 2029