PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

The study provides a TT-focused prospective analysis still rare in pediatric oncology. The outcomes indicate satisfactory tolerance and promising efficacy of TT, prompting an update of current treatment standards for several pediatric cancers.

Reference inhibitors (osimertinib-EGFR, ibrutinib-BTK, THZ1-CDK7, and THZ531-CDK12) reproduced the expected geometries and served as internal controls. Although no quantitative affinity was inferred, the consistent geometric feasibility supports their potential as structural templates for covalent-binding natural scaffolds. These results provide a qualitative, structure-based rationale for further chemoproteomic and enzymatic validation of NP-derived or hybrid compounds as potential leads in cancer therapy, expanding covalent chemical space beyond existing synthetic scaffolds.

The advent of targeted therapy, notably the first tyrosine kinase inhibitor (TKI) imatinib, has revolutionized the treatment landscape for GISTs...This commentary highlights discrepancies in the recommendations for managing GISTs as outlined in these major guidelines. Based on emerging new evidence from recent studies, the authors propose recommendations to be considered for inclusion in future guideline updates to optimize management strategies and ultimately improve the outcomes of patients with GISTs.

Our findings highlight the clinical relevance of integrating NGS into routine GIST management, particularly for the identification and interpretation of rare genetic variants. The study underscores the importance of data sharing and collective variant annotation to support accurate molecular classification, prognostic assessment, and therapeutic decision-making for individual patients.

INSM1 is highly expressed in human glioblastoma tumors and, during cortical development, in intermediate progenitor cells, which give rise to neurons. Remarkably, INSM1 knockdown in triple mutant NSCs and primary glioblastoma cells disrupts oncogenic gene expression and function and inhibits the in vivo tumorigenicity of triple mutant NSCs, highlighting the functional importance of an intermediate progenitor cell-like cell state in glioblastoma pathogenesis.

Immune profiling shows P2 as immunosuppressive, characterized by LGALS9 and M2 macrophages. Our proteogenomic analyses provide a molecular landscape of LMS, revealing biological insights, patient outcome stratification, and therapeutic targets.

This led to the in silico identification of a novel lead compound with a distinct thiazolopyridine-based scaffold and high predicted potency. Our findings demonstrate how integrated bioinformatic pipelines can dissect the complex landscape of GBM resistance, contextualize the roles of key oncogenes, and guide the rational design of potential new inhibitors.

Adult and embryonic MSCs exhibited overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminated in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SyS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.

VWF, PDGFRA and FCN1 were stably expressed in both groups, suggesting the existence of a conserved homeostatic regulatory network. In conclusion, this study reveals the cross-tissue functional heterogeneity of cell types shared by CRC and SP, suggests a set of potential pervasive regulators, and provides new perspectives for understanding the systemic effects of tumors and the microenvironmental mechanisms of sarcopenia.

Proteome-based receptor tyrosine kinase (RTK) pathway profiling suggests PDGFRA and ERBB2 (HER2) as potential candidates for targeted therapy. Our results provide unique proteomic contribution to the understanding of SPN biology and highlight differences from other pancreatic tumors.

P3, N=134, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2026 --> Dec 2026

Using a 73-gene panel, we characterized the molecular characteristics of GISTs and revealed a correlation with their clinical features. Moreover, KIT/PDGFRA-dependent and KIT/PDGFRA-independent mechanisms underlying resistance to imatinib were explored. Overall, our 73-gene panel is sufficient for clinical application in cases of GISTs.