Our results show that the multitargeted SRC TKI dasatinib significantly enhanced the efficacy of RET TKIs in RET fusion-positive (RET+) NSCLC and PTC cells...Importantly, synergy was also observed with eCF506 (NXP900), a next-generation clinical SRC inhibitor. Finally, both SRC TKIs restored sensitivity in selpercatinib-resistant RET+ PTC cells. These results elucidate RET and SRC signaling crosstalk in RET+ NSCLC and PTC, suggesting that co-inhibiting SRC has clinical potential in TKI-naïve and -resistant RET+ cancers.

P1, N=140, Recruiting, Nuvectis Pharma, Inc. | N=40 --> 140 | Trial completion date: May 2025 --> Jul 2027 | Trial primary completion date: Apr 2025 --> Mar 2027

P1, N=40, Recruiting, Nuvectis Pharma, Inc. | Trial primary completion date: Jan 2025 --> Apr 2025

P1, N=40, Recruiting, Nuvectis Pharma, Inc. | Trial completion date: Jan 2025 --> Apr 2025 | Trial primary completion date: Sep 2024 --> Jan 2025

Application of kinase activity prediction algorithms and interrogation of gene dependency and drug sensitivity databases predicted that the mechanistic target of rapamycin kinase (mTOR) and dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) represented potential therapeutic targets for the EMT and metabolism subtypes, respectively, and this was confirmed using selective inhibitors. Overall, our study provides novel, in-depth insights into GC proteomics, kinomics, and molecular taxonomy and reveals potential therapeutic targets that could provide the basis for precision treatments.

In contrast, in EC-specific Src-deficiency, VE-cadherin internalization is maintained, and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity.

P1, N=40, Recruiting, Nuvectis Pharma, Inc. | Not yet recruiting --> Recruiting | Initiation date: Jun 2023 --> Oct 2023

P1, N=40, Not yet recruiting, Nuvectis Pharma, Inc.

Data from drug combination screens with EGF816 and ceritinib indicate that dasatinib and agents disrupting microtubules act synergistically across many cell lines. Finally, we show that a higher-order-combination screen with 26 selected drugs in two resistant EGFR-mutant lung cancer cell lines identified active triplet combinations.

This study developed a robust IGS model for survival prediction of HCC patients, providing new insights into integrating tailored risk stratification with precise immunotherapy and screening potentially targeted agents.