APC

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 study investigated the prevalence and characteristics of germline mutations in 1094 Chinese colorectal cancer (CRC) patients using a 53-gene hereditary cancer panel. Pathogenic/likely pathogenic (P/LP) germline mutations were identified in 9.3% of patients, with mismatch repair (MMR) genes being the most frequently affected. Chinese patients showed lower frequencies of MUTYH and APC mutations but higher rates of MMR mutations compared to Western populations. Patients harboring germline P/LP mutations had significantly better progression-free survival, and a notable proportion of carriers lacked family history or were diagnosed after age 65. These findings highlight the need for population-specific genetic testing and screening strategies tailored for Asian populations.

This study demonstrates that MEK1/2 inhibitors, targeting the Ras-MAPK pathway, induce AXIN1 protein loss in colorectal cancer cell lines and patient-derived organoids. Unlike GSK3 inhibitors, this loss is not attributed to altered AXIN1 protein stability or post-translational modifications, nor to a significant reduction in its transcript levels. Analyses revealed that MEK1/2 inhibitors reduce global protein synthesis via an mTOR-associated pathway, an effect sufficient to cause AXIN1 loss. Co-treatment with tankyrase inhibitors was shown to partially prevent this AXIN1 reduction.