KRAS mutation

Histopathological evaluation may aid risk stratification alongside KRAS status. Prognostic assessment in clinical settings should take both TNM staging and KRAS status into account.

Furthermore, we validated the specificity of our approach by successfully detecting various mutations, including KRAS G12C, KRAS G12D, EGFR T790M and TP53 R273H, in simulated clinical samples. These findings highlight a reliable method for precise ctDNA detection, offering high specificity, selectivity, and accuracy, thus paving the way for potential cancer diagnostic application.

Mutational analysis further highlighted the significance of KRAS G12C, G12V, and G12D mutations, which were common between RCC and pancreatic metastasis. Our study provides critical insights into the statistically significant associations between metabolic disorders and malignancies, emphasizing the potential of tailored therapies alongside shared therapies in managing RCC and its progression to pancreatic metastasis.

In heavily pretreated patients with advanced solid tumors, E7386 demonstrated a manageable safety profile and a dose-dependent PK profile. PRs were noted in patients with small bowel carcinoma or desmoid tumor.

P2, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2027 --> Dec 2026

Molecular testing is feasible and may even be more successful in cytologic smears than in biopsies or resections. High diagnostic yield and rapid processing favor their integration into routine molecular workflows. The superior performance of smears may relate to reduced stromal content and minimal processing delays. Cytologic specimens showed 100% DNA QC success, even when RNA QC failed, supporting their reliability. Although RNA analysis had a modest failure rate, its overall success suggests it can be incorporated into routine testing, particularly as fusion-driven targets gain clinical relevance.

Alterations associated with the formation of a somatic-type malignancy and/or the development of cisplatin resistance include TP53 mutations or MDM2 gene amplifications as well as epigenetic alterations...Additionally, we will provide guidance on how to examine a testicular tumour specimen histopathologically to reach an accurate diagnosis. Finally, we will outline the importance of the content of a histopathological report for the urologists and oncologists.

The LNMRGS is a robust prognostic signature for CRC. NPR3 plays a key role in metastatic progression and chemoresistance, suggesting it as a potential therapeutic target.

The landmark approval of Sotorasib in 2021, the first covalent KRASG12C inhibitor, shattered this dogma, ushering in a new era of targeted therapy for KRAS-mutant cancers, which also has catalyzed an explosion of innovative strategies extending far beyond covalent G12C targeting...Additionally, it encompasses structure-activity relationship (SAR) investigations and activity optimization processes and pharmacokinetic properties studies of representative molecules. Furthermore, we critically evaluate existing challenges in developing small-molecule KRAS modulators while discussing emerging opportunities in overcoming on-target resistance, aiming to offer valuable insights and perspectives for future research in this rapidly evolving field.

Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.