Oncolytic viruses (OVs) are emerging as potential treatment options for cancer. Natural and genetically engineered viruses exhibit various antitumor mechanisms. OVs act by direct cytolysis, the potentiation of the immune system through antigen release, and the activation of inflammatory responses or indirectly by interference with different types of elements in the tumor microenvironment, modification of energy metabolism in tumor cells, and antiangiogenic action. The action of OVs is pleiotropic, and they show varied interactions with the host and tumor cells. An important impediment in oncolytic virotherapy is the journey of the virus into the tumor cells and the possibility of its binding to different biological and nonbiological vectors. OVs have been demonstrated to eliminate cancer cells that are resistant to standard treatments in many clinical trials for various cancers (melanoma, lung, and hepatic); however, there are several elements of resistance to the action of viruses per se. Therefore, it is necessary to evaluate the combination of OVs with other standard treatment modalities, such as chemotherapy, immunotherapy, targeted therapies, and cellular therapies, to increase the response rate. This review provides a comprehensive update on OVs, their use in oncolytic virotherapy, and the future prospects of this therapy alongside the standard therapies currently used in cancer treatment.

Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy’s efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed.

Background/Objectives: This study explores the application of vision transformers to predict early responses to stereotactic radiosurgery in patients with brain metastases using minimally pre-processed magnetic resonance imaging scans. The objective is to assess the potential of vision transformers as a predictive tool for clinical decision-making, particularly in the context of imbalanced datasets. Methods: We analyzed magnetic resonance imaging scans from 19 brain metastases patients, focusing on axial fluid-attenuated inversion recovery and high-resolution contrast-enhanced T1-weighted sequences. Patients were categorized into responders (complete or partial response) and non-responders (stable or progressive disease). Results: Despite the imbalanced nature of the dataset, our results demonstrate that vision transformers can predict early treatment responses with an overall accuracy of 99%. The model exhibited high precision (99% for progression and 100% for regression) and recall (99% for progression and 100% for regression). The use of the attention mechanism in the vision transformers allowed the model to focus on relevant features in the magnetic resonance imaging images, ensuring an unbiased performance even with the imbalanced data. Confusion matrix analysis further confirmed the model’s reliability, with minimal misclassifications. Additionally, the model achieved a perfect area under the receiver operator characteristic curve (AUC = 1.00), effectively distinguishing between responders and non-responders. Conclusions: These findings highlight the potential of vision transformers, aided by the attention mechanism, as a non-invasive, predictive tool for early response assessment in clinical oncology. The vision transformer (ViT) model employed in this study processes MRIs as sequences of patches, enabling the capture of localized tumor features critical for early response prediction. By leveraging patch-based feature learning, this approach enhances robustness, interpretability, and clinical applicability, addressing key challenges in tumor progression prediction following stereotactic radiosurgery (SRS). The model’s robust performance, despite the dataset imbalance, underscores its ability to provide unbiased predictions. This approach could significantly enhance clinical decision-making and support personalized treatment strategies for brain metastases. Future research should validate these findings in larger, more diverse cohorts and explore the integration of additional data types to further optimize the model’s clinical utility.

Colorectal cancer (CRC), a prevalent malignancy, is a significant global health concern. The intricate interplay of genetic mutations, inflammatory processes, and environmental factors underscores the complexity of CRC’s etiology. The human gut harbors a diverse microbial community that plays a key role in maintaining homeostasis and influencing various aspects of host physiology. Perturbations in the gut microbiome (GM) composition and function have been implicated in CRC carcinogenesis. This bidirectional relationship involves microbial contributions to inflammation, DNA damage, and immune modulation, shaping the tumor microenvironment (TME). Bacteriophages, viruses that infect bacteria, contribute to the microbiome’s diversity and function by influencing bacterial abundance and composition. These phages can impact host–microbiome interactions, potentially influencing CRC risk. Furthermore, they can be manipulated to transport targeted medication, without being metabolized. Antibiotics exert selective pressures on the gut microbiome, leading to shifts in bacterial populations and potential dysbiosis. Probiotics can modulate the composition and activity of the GM and could be considered adjunctive therapy in the treatment of CRC. Understanding the intricate balance between bacteriophages, antibiotics–probiotics, and the GM is essential for comprehending CRC etiology and progression.

Cancer immunotherapy increasingly relies on nucleic acid-based vaccines, yet achieving efficient and safe delivery remains a critical limitation. Polyplexes—electrostatic complexes of cationic polymers and nucleic acids—have emerged as versatile carriers offering greater chemical tunability and multivalent targeting capacity compared to lipid nanoparticles, with lower immunogenicity than viral vectors. This review summarizes key design principles governing polyplex performance, including polymer chemistry, architecture, and assembly route—emphasizing microfluidic fabrication for improved size control and reproducibility. Mechanistically, effective systems support stepwise delivery: tumor targeting, cellular uptake, endosomal escape (via proton-sponge, membrane fusion, or photochemical disruption), and compartment-specific cargo release. We discuss therapeutic applications spanning plasmid DNA, siRNA, miRNA, mRNA, and CRISPR-based editing, highlighting preclinical data across multiple tumor types and early clinical evidence of on-target knockdown in human cancers. Particular attention is given to physiological barriers and engineering strategies—including size-switching systems, charge-reversal polymers, and tumor-penetrating peptides—that improve intratumoral distribution. However, significant challenges persist, including cationic toxicity, protein corona formation, manufacturing variability, and limited clinical responses to date. Current evidence supports polyplexes as a modular platform complementary to lipid nanoparticles in selected oncology indications, though realizing this potential requires continued optimization alongside rigorous translational development.

Background: Survival prediction in patients with brain metastases remains a major clinical challenge, where timely and individualized prognostic estimates are critical for guiding treatment strategies and patient counseling. Methods: We propose a novel hybrid deep learning framework that integrates volumetric MRI-derived imaging biomarkers with structured clinical and demographic data to predict overall survival time. Our dataset includes 148 patients from three institutions, featuring expert-annotated segmentations of enhancing tumors, necrosis, and peritumoral edema. Two convolutional neural network backbones—ResNet-50 and EfficientNet-B0—were fused with fully connected layers processing tabular data. Models were trained using mean squared error loss and evaluated through stratified cross-validation and an independent held-out test set. Results: The hybrid model based on EfficientNet-B0 achieved state-of-the-art performance, attaining an R² score of 0.970 and a mean absolute error of 3.05 days on the test set. Permutation feature importance highlighted edema-to-tumor ratio and enhancing tumor volume as the most informative predictors. Grad-CAM visualizations confirmed the model’s attention to anatomically and clinically relevant regions. Performance consistency across validation folds confirmed the framework’s robustness and generalizability. Conclusions: This study demonstrates that multimodal deep learning can deliver accurate, explainable, and clinically actionable survival predictions in brain metastases. The proposed framework offers a promising foundation for integration into real-world oncology workflows to support personalized prognosis and informed therapeutic decision-making.