KRAS

This study investigated the dynamics of circulating tumor cells (CTCs) in 18 patients with advanced KRASG12C-mutated solid tumors treated with glecirasib, a KRASG12C inhibitor. Researchers observed an evolution in CTC subtypes (epithelial, mesenchymal, mixed) during treatment, particularly an increase in mixed CTCs at progression. Baseline CTC levels and their changes correlated with progression-free survival and overall survival. Furthermore, adding local radiotherapy for progressive lesions in patients with more than one CTC at progression significantly prolonged survival.

This prospective observational study assessed the utility of circulating tumor DNA (ctDNA) for mutational profiling and dynamic monitoring in 33 patients with metastatic colorectal cancer receiving palliative chemotherapy. ctDNA was detected in most patients at baseline, revealing frequent mutations in APC, TP53, KRAS, and PIK3CA. Good concordance was observed between plasma ctDNA profiles and tissue data. Longitudinal analysis showed the emergence of acquired mutations, particularly RAS mutations under anti-EGFR therapy, and correlated high ctDNA levels with shorter overall survival. These findings highlight ctDNA's potential to guide personalized treatment strategies and monitor resistance.

This study re-evaluates the clinicopathological and molecular features of nonampullary duodenal neoplasms with gastric phenotype, proposing a novel classification. Analyzing 105 lesions, researchers observed a predominance of low-grade tumors and frequent heterogeneity. Next-generation sequencing revealed recurrent mutations in GNAS, KRAS, and APC. MDM2 gene amplification was identified as a potential marker for histological progression in high-grade tumors. Despite morphological diversity, the prognosis was extremely favorable, with no metastases, supporting the reclassification as "gastric-type adenomas."

This retrospective study analyzed 120 cases of lung adenocarcinoma (LUAD) with malignant serous effusions (MSE) to characterize their clinicopathologic, molecular, and prognostic features. Pleural effusions were most common, but pericardial involvement was associated with the shortest overall survival. Molecular profiling revealed TP53 mutations and actionable alterations in genes such as EGFR, KRAS, BRAF, ALK, and ROS1. NKX2-1 (TTF-1) negativity and the absence of actionable alterations were independent adverse prognostic factors, with dual NKX2-1/CD274 (PD-L1) negativity defining the poorest prognosis subgroup. Immunotherapy-based regimens and tyrosine kinase inhibitors showed varying survival benefits.

This study analyzed the genomic profile of 480 patients with metastatic adenocarcinoma of unknown primary (ACUP) using the FoundationOne CDx platform. The most frequent mutations included TP53, KRAS, and CDKN2A. Results showed that GNAS and PIK3CA mutations were associated with better overall survival. Conversely, ARID1A and NOTCH1 alterations were linked to a worse prognosis. These findings highlight the significance of specific genomic alterations as prognostic markers in ACUP.