Among the derivatives, compound 3k showed the highest binding affinity for VEGFR-2 (- 8.18 kcal/mol) and BRAF (- 8.64 kcal/mol), surpassing the control drugs etoposide (- 8.00 kcal/mol) and dabrafenib (- 8.15 kcal/mol) respectively. ADMET analysis confirmed good intestinal absorption, limited blood-brain barrier penetration, non-toxicity, acceptable total clearance, and compliance with Lipinski's rule. Overall, the study suggests that pyrazole-modified catalpol derivatives, especially compound 3k, are promising multi-target inhibitors for pancreatic and esophageal cancers, justify further in-vitro and in-vivo studies.

Overall, liposomal co-delivery maintains DOX cytotoxicity while strengthening G₁/S checkpoint blockade and increasing programmed cell death, with partial moderation of DNA fragmentation. These in-vitro data motivate stability optimization and in-vivo evaluation in CRC models.

This platform comprises GIC-targeting exosomes that carry siRNA for Notch1 and mitoxantrone to reduce the stemness of GICs and kill residual GICs and glioma cells, respectively, and an immune activator (interleukin-12), which can remodel the immunosuppressive tumor microenvironment, ultimately suppressing postoperative GBM relapse. Our work provides a perspective into the effective inhibition of postresection recurrence of GBM.

P3, N=60, Active, not recruiting, University of California, San Francisco | Recruiting --> Active, not recruiting

P3, N=559, Completed, Sun Yat-sen University | Recruiting --> Completed

Taken together, endothelial TFEB protects against EC damage and cardiac dysfunction, constituting a potential target for treating cardiotoxicity induced by DOX. Our study provides new mechanistic insights into cardiotoxicity associated with chemotherapy.

Besides, according to in vivo studies, the combination of RSL3 and Dox further suppressed BC tumor growth without inducing significant adverse effects. On these accounts, RSL3 makes BC cells more sensitive to Dox by inducing glycolytic dysfunction, implying that RSL3/Dox co-treatment could be a viable therapeutic approach for BC patients.

P1/2, N=52, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P1/2, N=43, Not yet recruiting, Sun Yet-Sen University Cancer Center

P3, N=228, Recruiting, Sun Yat-sen University | Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jun 2026

P2, N=21, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=46 --> 21 | Trial primary completion date: Jan 2027 --> Jun 2025

Doxorubicin (DOX) forms stable π-π stacking complexes with PDA, creating a versatile chemotherapeutic delivery platform...We hypothesize that this integrated approach will demonstrate enhanced antitumor efficacy while promoting functional bone reconstruction. Comprehensive in vitro evaluations will elucidate the underlying mechanisms and provide preclinical validation for this precision oncology strategy.