EGFR (Epidermal growth factor receptor)

P2, N=50, Not yet recruiting, Fred Hutchinson Cancer Center

P1/2, N=70, Terminated, VBI Vaccines Inc. | Recruiting --> Terminated; VBI Bankruptcy

Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients.

PDC treatment significantly suppresses tumor growth in in vivo KRAS mutant xenograft model, demonstrating superior efficacy compared with cetuximab-based regimens and controls, without observable body weight loss. This strategy uses EGFR as a delivery portal instead of a signaling target, enabling KRAS independent anti-tumor activity. These findings indicate a non-canonical EGFR mediated delivery approach with potential translational relevance for the treatment of therapy resistant CRC.

Integration with synNotch receptors and chimeric antigen receptors (CARs) further allows dual-input regulation of downstream responses, including gene expression, cytokine release, and cytotoxicity. Together, these results establish extrabody as a versatile and generalizable interface for externally controlled cellular communication and synthetic signaling.

Ficerafusp alfa plus pembrolizumab demonstrated favorable safety and tolerability with promising antitumor activity in the first-line treatment of R/M HNSCC, particularly in those with HPV-negative tumors.

nCIT establishes a new standard of care for resectable non-small cell lung cancer, offering improved pathological and survival outcomes while preserving surgical safety. Future research should focus on unresolved issues such as patient selection, biomarker integration and the role of adjuvant immunotherapy to refine personalized treatment strategies.

Furthermore, we detail how GnT-V orchestrates the epithelial-mesenchymal transition (EMT) and cytoskeletal remodeling via the RhoA/Rac1 axis. By integrating these signaling networks with the enzyme's regulatory environment, we provide a comprehensive roadmap of GnT-V pathogenesis and propose that targeting the GnT-V/GnT-III balance represents a promising strategy for precise cancer diagnosis and therapy.

This study identifies bulk transcriptome-defined groups and reveals EGFR-associated malignant cell programs linked to distinct microenvironmental interaction patterns. The EGFR-high malignant cell state features proliferative and angiogenic programs, while the EGFR-low malignant cell state shows enhanced immune infiltration. These findings provide molecular evidence for precision classification and subtype-specific therapeutic strategies.

However, current standard of care treatments such as surgical resection, radiotherapy, temozolomide, and tumor treating fields have reached a therapeutic plateau, highlighting the urgent need for new therapeutic strategies...We further synthesize recent advances in spatial and longitudinal profiling technologies to describe the dynamic tumor immune ecosystem. We discuss how spatial compartmentalization and evolutionary processes collectively drive immune escape and therapeutic resistance, and highlight emerging strategies including adaptive immunotherapy, precision targeted delivery, and multimodal monitoring to overcome these challenges.

It also outlines next generation directions, including higher order multispecific constructs, conditionally active antibodies, and payload conjugated multispecific formats. To consolidate these agents as an established therapeutic modality in oncology, priority should be given to rigorous understanding of mechanisms of action and toxicity, alongside rational optimisation of construct design and dosing, supported by robust prospective translational programmes.

Several derivatives, including spirooxindole-pyrrolidine hybrids, thiazolo-pyrrolidine-spirooxindolines, and dispirooxindolines, demonstrate superior activity compared with cisplatin and doxorubicin. Emerging synthetic strategies, particularly multicomponent reactions and click chemistry, further expand the scope of these molecules. Collectively, current findings underscore their potential as anticancer agents and the importance of future in vivo and pharmacokinetic studies to advance clinical translation.