Messenger RNA (mRNA)-based therapeutics have emerged as a programmable platform with expanding relevance to neuro-oncology, where intracranial disease control remains difficult to achieve. Recent successes in systemic oncology have renewed interest in applying these approaches to primary and metastatic brain tumors. We performed a narrative synthesis of clinical, translational, and mechanistic studies evaluating mRNA-guided therapeutic strategies in glioblastoma (GBM) and brain metastases (BrM). In GBM, clinical experience has been dominated by dendritic cell-mRNA vaccination, which consistently demonstrates feasibility and the ability to induce antigen-specific immune responses, but only limited and inconsistent intracranial efficacy. This discrepancy reflects multiple converging constraints, including profound intratumoral immune suppression, heterogeneous blood-brain and blood-tumor barrier permeability that limits effector access and delivery exposure, and treatment-related immunosuppression, particularly corticosteroid use. Emerging mRNA modalities, including delivery-targeted mRNA systems and mRNA-enabled immune programming strategies such as transient chimeric antigen receptor (CAR) expression or local immunomodulatory payload delivery, offer theoretical advantages in localization, controllability, and safety. However, their translation remains constrained by biodistribution limitations, intratumoral heterogeneity, and uncertainty regarding reliable intracranial exposure across infiltrative tumor compartments. In brain metastases (BrM), systemic mRNA vaccine strategies appear more transferable because they rely primarily on peripheral immune priming rather than direct intracranial payload delivery, aligning with tumor types that already demonstrate responsiveness to immune checkpoint blockade. Nevertheless, intracranial efficacy remains influenced by lesion-level heterogeneity, including variable blood-tumor barrier permeability, differences in immune microenvironment permissiveness across lesions, and discordant intracranial versus extracranial treatment responses. Collectively, these findings indicate that while mRNA platforms are biologically active and mechanistically versatile, durable intracranial benefit depends on matching therapeutic modality to disease-specific delivery, immune, and microenvironmental constraints. mRNA-based therapies are biologically active and feasible in neuro-oncology, but durable intracranial benefits will require disease-specific strategies that explicitly address CNS barriers. Progress will depend on mechanism-driven combinations, steroid-aware trial design, and endpoints that directly assess intracranial immune engagement.
Objective: To develop and validate a machine learning–based MRI radiomics model for predicting the risk of non-pathological complete response (non-pCR) following neoadjuvant chemotherapy in breast cancer, to identify independent influencing factors. Methods: A total of 400 consecutive breast cancer patients were randomly divided into training and validation sets at a 7:3 ratio. Baseline clinicopathological variables, functional magnetic resonance imaging (MRI) parameters, tumor-infiltrating lymphocytes (TILs), and longitudinal MRI radiomics scores were collected. Variables were selected using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression. Random forest, support vector machine, and logistic regression models were constructed and evaluated using area under the curve (AUC), calibration, decision curve analysis, and SHapley Additive exPlanations (SHAP) interpretation. Results: Multivariate logistic regression confirmed all six factors (Ki-67 proliferation index, maximum tumor diameter, apparent diffusion coefficient (ADC) value, initial enhancement rate, tumor-infiltrating lymphocytes (TILs), and radiomics score) as independent predictors of non-pCR (P < 0.05). The random forest model showed the numerically highest AUC, with an AUC of 0.835 [95% confidence interval(CI): 0.767–0.904] in the training set and 0.745 (95% CI: 0.597–0.893) in the validation set, outperforming logistic regression (training: 0.805; validation: 0.717) and support vector machine (training: 0.792; validation: 0.702). SHAP analysis revealed that feature contributions, in descending order, were as follows: radiomics score, ADC value, initial enhancement rate, TILs, Ki-67 proliferation index, and maximum tumor diameter. SHAP analysis identified radiomics score, ADC value, and initial enhancement rate as the leading contributors. Conclusions: The random forest model constructed in this study, integrating MRI radiomics and functional imaging parameters, exhibits acceptable discrimination and calibration for predicting pathological response to neoadjuvant chemotherapy in breast cancer.
Objective: The IVOPAK II study (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer) prospectively evaluated the risk (postoperative complications, mortality) and benefit (overall survival) of multimodal treatment with secondary metastasis resection for initially nonresectable metastatic colorectal carcinoma. Patients and Methods: A total of 40 patients from 10 centers were enrolled. Patients with quintuple wildtype (K-RAS, N-RAS, BRAF, PIK3CA, ERBB2, MSS) received FOLFIRI plus cetuximab, while patients with RAS-mutation (K-RAS or N-RAS, MSS) received FOLFIRI plus bevacizumab. CT scans were presented at two-month intervals to the interdisciplinary tumor board at the University Hospital Erlangen to assess potentially curative secondary metastatic resection. After a median follow-up of 32 months, outcomes of the multimodally (chemotherapy treatment plus metastasis resection) and the palliatively (only chemotherapy treatment) treated patients were compared. Results: The rate of secondary metastasis resection was 45% (18/40). Overall survival was significantly longer in the multimodal treatment group compared to the palliative treatment group (median 61 vs. 22 months, p=0.002), this also applied to progression-free survival (median 39 vs. 11 months, p=0.018). Clavien-Dindo grade ≥3 morbidity occurred in 28% (5/18) of patients, and 90-day mortality was 6% (1/18). Univariate analyses revealed a significant improvement in overall survival among patients with ECOG performance status 0, solitary metastatic site and multimodal treatment. In multivariate analysis, the ECOG performance status proved to be an independent prognostic factor. Conclusion: Following palliative biomarker-stratified first-line treatment for nonresectable metastatic colorectal carcinoma, the multimodal approach with secondary metastatic resection demonstrated a significant survival benefit.
Introduction: Screening for hepatocellular carcinoma (HCC) aims to detect early tumors, with a positive impact on survival. In clinical practice there are several challenges on the application of HCC screening: patients with unknown liver disease, poor patient adherence or problems in the health care system, leading to an underperformance. We aim to evaluate the performance of the HCC screening, the reasons of missed or delayed diagnosis, and prognostic implications in patients with HCC in a tertiary center. Methods: Retrospective study including patients with an HCC diagnosis, that have been discussed by a liver tumors board from 2020 to 2023 in a tertiary hospital. HCC screening was defined according to the EASL recommendations. Considering the target population for screening, subgroups were considered and compared: (a) diagnosed through screening; (b) missed screening due to suboptimal patient adherence and/or systemic healthcare inefficiencies; (c) undiagnosed advanced chronic liver disease (uACLD), that would have indication for surveillance if already diagnosed. For patients diagnosed through screening, we considered a margin of 2 months (8 months) as “complete surveillance” and between 8 to 12 months as “incomplete surveillance”. To access the survival benefit, we compared the overall survival of the screened population and those do not diagnose through screening. Results: We included 174 patients, 136 had advanced chronic liver disease (ACLD): 70% Child-Pugh (CP) A; 20% CP B; 10% CP C. The most common etiologic factor was excessive alcohol consumption (37%). The proportion of patients diagnosed in screening was 26%. Regarding Barcelona Clinic Liver Cancer (BCLC) stage at diagnosis, 4% BCLC-0, 37% BCLC-A, 10% BCLC-B, 33% BCLC-C and 15% BCLC-D. Patients in subgroup (a) had HCC diagnosed at earlier stages (BCLC-0 and BCLC-A). The subgroup (c) had a higher proportion CP B and C (p = 0.008), vascular invasion (p = 0.01), extrahepatic involvement (p = 0.052) and hepatic dysfunction according to ALBI score (p < 0.001) at time of diagnosis. Overall survival was significantly higher for screened group. Conclusion: In our cohort, only about a quarter of HCC cases were diagnosed through screening, with impact on survival. Among patients with indication for screening, only one third achieved diagnostic yield. Our findings emphasize the need to improve HCC screening strategies and the pivotal role of primary care in the early diagnosis of underlying liver disease.
Cisplatin remains a cornerstone of head and neck cancer (HNC) treatment, yet resistance frequently undermines therapeutic efficacy. Emerging evidence implicates Fusobacterium nucleatum, enriched in the tumour microbiome, in promoting chemoresistance via molecular and microenvironmental mechanisms. This review synthesises evidence from PubMed, Scopus, and Web of Science (January 2015-September 2025) examining F. nucleatum’s contribution to cisplatin resistance in HNC. Cisplatin resistance involves tumour-intrinsic pathways, such as nucleotide excision repair, homologous recombination, and ATP7B-mediated drug efflux. F. nucleatum indirectly enhances resistance via Wnt5a/Ca²⁺–NFATc3 signalling, downregulation of p53 and E-cadherin, and activation of the NLRP3 inflammasome, which recruits myeloid-derived suppressor cells. It also amplifies inflammation and chemoresistance by escalating the senescence-associated secretory phenotype, promoting a tumour-supportive microenvironment. These findings highlight microbiome host crosstalk as a therapeutic target, suggesting that microbiota-directed strategies alongside cisplatin may improve outcomes in resistant HNC.
