Journal of Personalized Medicine

Objective(s): To delineate the somatic mutational landscape of follicular thyroid carcinoma (FTC) from a large, real-world cohort to identify molecular subtypes and actionable targets for personalized therapeutic interventions. Methods: Genomic and clinical data for 168 FTC samples were retrieved from the AACR Project GENIE^® registry via cBioPortal. This study assessed mutation frequencies, copy number alterations, and subgroup differences (primary vs. metastatic; adult vs. pediatric) using statistical tests. Results: NRAS was the most common mutation (33.9%), followed by TERT (22.6%), DICER1 (15.5%), HRAS (11.9%), and PTEN (10.7%). DICER1 mutations were significantly enriched in pediatric cases (44.4% vs. 4.6% in adults, p < 0.001), while TERT mutations were exclusive to adults (42%). NRAS mutations were more frequent in metastatic tumors (42.4%) than primary tumors (29.2%). Conclusions: FTC tumorigenesis is driven by distinct molecular pathways, with significant heterogeneity between pediatric and adult patients as well as primary and metastatic disease. These findings underscore the necessity of molecular profiling for patient stratification and provide a strong rationale for developing personalized treatment strategies to improve clinical outcomes.

Objective(s): To characterize the somatic mutational landscape of laryngeal squamous cell carcinoma (LSCC) using AACR Project GENIE data to identify potential biomarkers for tumor progression and guide precision therapy. Methods: Clinical and genomic data from 135 LSCC samples (primary and metastatic) were analyzed from the AACR Project GENIE database. Mutations were compared by tumor site and gender using chi-squared and Mann–Whitney U tests; co-occurrence and mutual-exclusivity analyses were performed. Results: TP53 mutations were most common (89.6%), followed by KMT2D (27.4%), FAT1 (20.7%), and NOTCH1 (20.7%). CDK8 mutations were enriched in females (p = 0.011) and ATP8B1 in males (p = 0.013). DMD mutations characterized primary tumors (p = 0.049), whereas ATP8B1 and SAMD9L were linked to metastases (p < 0.001). The cohort was 85.9% male and 71.5% White; 59.2% of samples were primary and 39.2% recurrent/metastatic. Co-occurrence analysis identified distinct molecular subtypes. The identification of distinct molecular subtypes and gender-specific mutations, such as CDK8 in females and ATP8B1 in males, suggests potential avenues for tailored therapeutic interventions. Conclusions: LSCC exhibits marked genetic heterogeneity dominated by TP53 alterations. ATP8B1 and SAMD9L mutations may mark metastatic disease, and gender-specific mutations suggest avenues for personalized therapy. These insights support development of targeted strategies, including immunotherapies such as pembrolizumab in TP53-altered tumors. These insights into the genomic heterogeneity of LSCC lay the groundwork for developing targeted therapeutic strategies and patient stratification, ultimately advancing a personalized medicine approach to this disease.

Liver diseases, including fibrosis, viral hepatitis, hepatocellular carcinoma, and monogenic genetic disorders, represent a major global health burden with limited therapeutic options and frequent systemic toxicity from conventional treatments. Nanovesicle-based drug and gene delivery systems offer targeted approaches that may improve therapeutic precision and reduce off-target effects. This review aims to evaluate the promise and comparative potential of three key nanovesicle platforms—lipid nanoparticles (LNPs), extracellular vesicles (EVs) and liposomes—for drug and gene delivery in liver disease therapy. A systematic search of peer-reviewed studies published in electronic databases was performed, focusing on preclinical and clinical research investigating the use of LNPs, EVs and liposomes for hepatic drug or gene delivery. Studies were analyzed for vesicle composition, targeting efficiency, payload capacity, therapeutic outcomes, and reported limitations. The analysis indicates that LNPs demonstrate strong efficiency in nucleic acid encapsulation and delivery, supported by growing clinical translation. EVs show promising biocompatibility and innate targeting to hepatic cells but face challenges in large-scale production and standardization. Liposomes remain versatile and well-characterized platforms capable of carrying diverse therapeutic molecules, though rapid clearance can limit their efficacy. Together, these nanovesicle systems hold considerable potential for advancing targeted drug and gene therapies in liver disease. Future work should focus on improving stability, manufacturing scalability, and cell-specific targeting to support clinical translation.