Search

IntroductionIn the evolving healthcare landscape, precision medicine's rise necessitates adaptable doctoral training. The European Union has recognized this and promotes the development of international, training-focused programmes called Innovative Training Networks (ITNs). In this article, we introduce TranSYS, an ITN focused on educating the next generation of precision medicine researchers. In an ambition to go beyond describing the consortium goals, our article explores two key aspects of ITNs: the training and collaboration.MethodsUsing self-report questionnaires, we evaluate the scientific, professional, and personal growth of ESRs over the duration of the ITN and investigate whether this can be linked to network activities.ResultsOur quantitative analysis approach reveals substantial improvements in scientific, professional, and social skills among young researchers facilitated by the engagement in this interdisciplinary network. We provide case studies underlining the advantages of collaborative environments, featuring innovative scientific exchange within TranSYS.DiscussionWhile challenging, ITNs foster positive growth in young researchers, yet exhibit weaknesses such as balancing stakeholder interests and partner commitment. We believe this study may benefit a variety of stakeholders, from prospective ITN creators to industry partners, to design better sustainable training networks going forward.

IntroductionThe incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis.MethodsTo that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors.ResultsOur results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings.ConclusionIn conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.

Introduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification.Methods: Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement.Results: Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma.Conclusions: This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.

Brain metastases are the most common tumors of the central nervous system (CNS). Incidence rates vary according to primary tumor origin, whereas the majority of the cerebral metastases arise from primary tumors in the lung (40–50%). Brain metastases from lung cancer can occur concurrently or within months after lung cancer diagnosis. Survival rates after lung cancer brain metastasis diagnosis remain poor, to an utmost of 10 months. Therefore, prevention of brain metastasis is a critical concern in order to improve survival among cancer patients. Although several studies have been made in order to disclose the genetic and molecular mechanisms associated with CNS metastasis, the precise mechanisms that govern the CNS metastasis from lung cancer are yet to be clarified. The ability to forecast, which patients have a higher risk of brain metastasis occurrence, would aid cancer management approaches to diminish or prevent the development of brain metastasis and improve the clinical outcome for such patients. In this work, we revise genetic and molecular targets suitable for prediction of lung cancer CNS disease.