We identify the microtubule targeting agents lexibulin, colchicine, and combretastatin A-4 as three compounds that bind to the colchicine-binding pocket of the a/b tubulin dimer, and which show increased efficacy in a P47S liver cancer cell line compared to parental cells with WT p53. We find evidence for an unusual mechanism underlying this increased efficacy: our data indicate that the P47S variant shows increased ability to bind to the peptidyl-prolyl isomerase PIN1; this leads to decreased PIN1-cyclin D1 complexes in P47S cells, along with increased cell cycle arrest in response to lexibulin. IMPLICATIONS: These findings support the growing literature that particular mutant forms of TP53 may have specific therapeutic vulnerabilities that can be targetable; improved understanding of these unique vulnerabilities can lead to improved understanding of p53 function.

P2, N=14, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Interim analysis indicated limited efficacy

P3, N=100, Recruiting, Steba Biotech S.A. | Trial primary completion date: Jun 2025 --> Mar 2026

SCHEMBL4796824, a BPR0L075 derivative with antitumor properties, targets tubulin's colchicine binding site and induces DNA damage response in ovarian cancer...Notably, these effects were more pronounced in c-MYC amplified SK-OV-3 cells. In summary, SCHEMBL4796824 disrupts the canonical Wnt/β-catenin signaling, inducing DNA damage, and inhibits the Wnt/β-catenin/c-MYC axis, triggering cellular senescence in a pathway-dependent manner, hinting at a novel therapeutic approach.

P2, N=64, Completed, Benha University

P1, N=13, Completed, Massachusetts General Hospital | Recruiting --> Completed | N=30 --> 13 | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025

We identified BAP1 as a potential predictive biomarker for JX-594 treatment and explored its underlying mechanisms. However, given that the study used immunodeficient models, the findings reflect tumor-intrinsic interferon responses and require further validation in immunocompetent models to assess immune microenvironment modulation and clinical relevance.

P1, N=30, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2025 --> Jul 2025

It also regulated apoptosis-related proteins poly(ADP-ribose) polymerase (PARP) and caspase-3 in HSFs. These findings suggest that CYT997 has potential as a targeted therapy for hypertrophic scars by inducing apoptosis in HSFs and reducing fibrotic activity.

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

P1, N=17, Completed, Columbia University | Recruiting --> Completed | N=40 --> 17 | Trial completion date: Sep 2025 --> Jun 2024

Vascular-targeted photodynamic therapy (VTP) with WST11 is a non-surgical tumor ablation approach that is currently being tested in a phase 3 clinical trial for the treatment of upper tract urothelial cancer...Moreover, VTP therapy prolonged the survival of mice bearing orthotopic tumors compared with the untreated control. These results suggest that VTP can selectively ablate malignant tumors in the bladder and promote a robust anti-tumor response in a mouse model that can further augment the therapeutic outcome.