EGFR expression

Histopathological analysis confirmed that therapeutic efficacy was driven by a significant reduction in EGFR protein levels. Our findings establish Hsp90-mediated stabilization of monomeric EGFR as a novel resistance mechanism and provide a translational rationale for employing low-dose Hsp90 inhibition in combination with cetuximab to improve clinical outcomes for HNSCC patients currently lacking effective targeted options.

Quantitative analysis revealed that EGFR-BsTe secretion abrogated EGFR upregulation and enhanced B7-H3 downregulation in a target-dependent manner; however, efficacy was diminished when the CAR-Target (B7-H3) was absent on a substantial fraction of tumor cells. Our findings suggest that arming B7-H3 CAR-T cells with EGFR-targeting bispecific engagers represents a promising strategy to overcome antigen heterogeneity and improve therapeutic outcomes for GBM patients.

P2, N=30, Not yet recruiting, HuiKai Li

Panitumumab was complexed to 197gHg/197mHg after conjugation to a bifunctional chelator or labeled directly with 197gHg/197mHg. These radioimmunoconjugates bound specifically to EGFR on human breast cancer cells and caused DNA double-strand breaks that decreased their clonogenic survival. The radioimmunoconjugates localized in EGFR-overexpressing MDA-MB-468 tumours in mice but there was high kidney uptake, suggesting in vivo release of some 197gHg/197mHg. Competition between complexation of 197gHg/197mHg to a bifunctional chelator and binding to endogenous mercury binding sites in panitumumab presents challenges for radiolabeling and may explain the apparent release of some 197gHg/197mHg in vivo. Alternative labeling strategies such as a 2-step method involving conjugation of the preformed 197gHg/197mHg bifunctional chelator to panitumumab could be explored to address these challenges.

In advanced/metastatic NSCLC with PD-L1 ≥ 50% and no EGFR/ALK alterations, first-line pembrolizumab demonstrates outcomes consistent with the pivotal trial and with published real-world evidence. The findings confirm that PS-ECOG ≥2 and prior PPI exposure are predictors of shorter OS, and that the development of toxicity during treatment is significantly associated with longer survival.

Survival analysis confirmed inferior outcomes in PDSCC (mean survival 1.27 years) versus WDSCC (3.28 years, p < 0.001). PDSCC exhibits aggressive pathology and compromised QOL, underscoring the need for early recognition and biomarker-based prognostication.

LIEE exhibits significant anti-osteoporotic effects through a multi-targeted mechanism involving modulation of ER/OPG/RANKL signalling, suppression of inflammation and oxidative stress, and regulation of key molecular targets. These outcomes propose that LIEE could help as a capable phytotherapeutic candidate for the management of postmenopausal osteoporosis and warrant more clinical exploration.

Using a large-scale Japanese genomic panel dataset, we characterized the molecular alterations associated with S/DD. S/DD frequently exhibits low Nectin-4 expression and basal-like molecular features, which may have implications for treatment selection and inform future therapeutic strategies.

Integrated profiling of TETs reveals distinct genomic, transcriptomic, and immune features across subtypes of TETs and identifies potentially actionable therapeutic targets that may inform future treatment strategies.

Molecular docking studies were performed on representative active compounds to rationalize observed biological activity and characterize key interactions within the ATP-binding sites of EGFR and B-RAF kinases. Collectively, these findings identify khellin-derived benzofuran-pyrazoline hybrid systems as promising candidates for targeting kinases and as potential anticancer agents, providing a rational basis for further structural optimization and mechanistic investigation.

P2, N=39, Not yet recruiting, Anhui Provincial Cancer Hospital

Although the initiation of cytotoxicity was kinetically slower than the αCD3 scFv counterpart, αTCR VHH CSANs achieved comparable end point cytotoxicity across multiple antigen densities, as well as in 3D tumor spheroids. Through this study we demonstrate the applicability of nanobodies as T-cell targeting domains, enhanced specificity and safety of moderate affinity T-cells binders and the diversification of T-cell targeting epitopes without compromising the efficacy of TCEs.