Furthermore, MD simulations introducing an additional dovitinib molecule to the FGFR1-dovitinib complex indicated the potential for weak and transient interactions in the preferred interaction regions on the FGFR1 surface. These findings highlight the multifaceted nature of kinase-inhibitor interactions and provide valuable biophysical insights that may contribute to future drug discovery efforts targeting receptor tyrosine kinases.

P1/2, N=139, Active, not recruiting, Alcon Research | Trial primary completion date: Oct 2027 --> May 2027

P1/2, N=139, Active, not recruiting, Alcon Research | Recruiting --> Active, not recruiting

Four protein kinase inhibitors, R547, GDC-0879, JNJ-7706621 and ABT-869 were found to bind hPIP5K1α via a stable complex formation. The hit molecules display favorable ADME properties and are predicted to be non-carcinogenic. The hit molecules in particular R547, have better binding free energies compared to reference molecule, ISA-2011B.

Herein, we reported an ultrasound (US)-controllable all-in-one dissolving microneedle (dMN) platform that integrated a ROS-cleavable prodrug, formed by conjugating the VEGF inhibitor linifanib, with ROS-responsive liposomes encapsulating the sonosensitizer MnTCPP (Mn@CTL-LPs dMNs)...This spatiotemporally controllable activation ensured high therapeutic precision and safety. Overall, this work presented a noninvasive and US-triggered strategy to potentiate sonodynamic immunotherapy for melanoma.

Clinical data further verified that high ZEB1 expression is associated with poor prognosis in RCC and that ZEB1 promotes tumor progression by regulating SCD1 to activate the Wnt signaling pathway. In conclusion, APS enhances the sensitivity of RCC to sunitinib by targeting the ZEB1-SCD1-Wnt axis, thus providing a theoretical basis for the clinical application of this combined therapy.

In vivo, both PDGFRα antibody neutralization and pharmacological inhibition with imatinib significantly attenuated DBP-induced hepatic fibrosis and inflammatory gene expression, confirming PDGFRα's central role in DBP toxicity...Collectively, these findings identify PDGFRα as a mechanistic nexus linking DBP and PS-NPs exposure to hepatic fibrosis and highlight its potential as a therapeutic target for environmentally induced liver disease. The results further underscore the importance of co-exposure paradigms in evaluating the health risks of complex contaminant mixtures.

P2, N=21, Recruiting, Sun Yat-sen University

P4, N=30, Not yet recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

We report a case of a 60-year-old male who developed intra-abdominal desmoid tumors five years after undergoing laparoscopy and endoscopy cooperative surgery (LECS) for gastric GIST, followed by adjuvant imatinib therapy...Histopathological confirmation remains crucial for accurate diagnosis. Surgical resection is the primary treatment for symptomatic desmoid tumors, but given their high recurrence rate, long-term follow-up and a multidisciplinary approach are essential for optimal management.

Surveillance MRI at 3 months postoperatively revealed local recurrence, prompting combination therapy with sunitinib (VEGF inhibitor) and sintilimab (anti-PD-1 antibody). Follow-up imaging demonstrated significant regression at 1 month, with no evidence of disease progression at 12-month reassessment.

Importantly, PRKAB2 overexpression significantly restored sensitivity to tyrosine kinase inhibitors (TKIs) in sunitinib-resistant RCC cells...Overall, our findings identify PRKAB2 as a critical tumor suppressor in RCC, regulating both protein-protein interactions and lipid metabolism to suppress mitophagy. Targeting PRKAB2-associated pathways may provide a promising therapeutic strategy to enhance treatment efficacy and overcome drug resistance in RCC.