Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life.

Photodynamic therapy (PDT) represents a promising non-antibiotic strategy for addressing bacterial and fungal infections, particularly in the context of increasing antimicrobial resistance and biofilm-associated disease. PDT is based on the light-induced activation of photosensitizers, leading to the generation of reactive oxygen species (ROS), including singlet oxygen (¹O₂), which induce oxidative damage to multiple microbial targets. Unlike conventional antimicrobial drugs that often act through specific molecular pathways, antimicrobial PDT produces simultaneous damage to membranes, proteins, nucleic acids, and extracellular biofilm components, thereby reducing the probability of resistance development. This review critically analyzes the cellular, biochemical, and biophysical determinants that govern PDT selectivity toward bacterial and fungal cells in comparison with mammalian host tissues. Particular attention is given to photosensitizer localization, membrane interactions, photobleaching, oxygen dependence, light penetration, and the balance between Type I and Type II photochemical mechanisms. The review provides a comparative overview of major molecular photosensitizer classes, including phenothiazines, porphyrins, chlorins, phthalocyanines, xanthene dyes, natural polyphenols, endogenous compounds, and advanced targeted photosensitizers. In addition, this review distinguishes molecular photosensitizers from nanotechnology-based platforms and delivery systems. Nanoparticles, polymeric carriers, hydrogels, and light-activated coatings are discussed not only as photosensitizer delivery tools, but also as systems that modulate aggregation, improve localization, enhance biofilm penetration, and enable surface-confined ROS generation. ROS are capable of causing phototoxic effects wherever they are located. Unless selectively accumulated by target organisms, there can be systemic phototoxicity. Overall, PDT should be regarded as a modular antimicrobial platform in which photosensitizer chemistry, formulation, light delivery, oxygen availability, and infection biology must be co-optimized. Although further studies are required to address clinical translation, regulatory complexity, material safety, and standardized treatment protocols, PDT offers a scientifically robust and clinically relevant approach that may complement conventional antibacterial and antifungal therapies, especially in localized, biofilm-associated, and device-related infections.

Drug discovery is a complex and multi-stage process that requires advanced analytical technologies capable of accelerating preclinical evaluation and improving the precision of therapeutic design. The combination of fluorescence and magnetic resonance imaging (MRI) within multimodal imaging plays an increasingly important role in modern pharmacokinetics, integrating the high molecular sensitivity of fluorescence with the non-invasive anatomical visualization offered by MRI. Fluorescence enables real-time monitoring of cellular processes, including drug–target interactions and molecular dynamics, whereas MRI provides detailed structural information on tissues without exposure to ionizing radiation. Hybrid probes—such as superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with near-infrared (NIR) fluorophores or gadolinium-based complexes linked to optical dyes—enable simultaneous acquisition of molecular and anatomical data in a single examination. These multimodal systems are being explored in oncology, neurology, and cardiology, where they support improved visualization of tumor biology, amyloid pathology, and inflammatory processes in vascular disease. Although multimodal imaging shows great promise for enhancing pharmacokinetic and pharmacodynamic studies, several challenges remain, including the potential toxicity of heavy-metal-based contrast agents, limited tissue penetration of fluorescence signals, probe stability in vivo, and the complexity and cost of synthesis. Advances in nanotechnology, particularly biodegradable carriers and manganese-based MRI contrasts, together with the integration of artificial intelligence algorithms, are helping to address these limitations. In the future, fluorescence–MRI hybrid imaging may become an important tool in personalized medicine, supporting more precise therapy planning and reducing the likelihood of clinical failure.

Cetuximab and panitumumab are anti-EGFR monoclonal antibodies widely used for the treatment of colorectal cancers. However, due to various mechanisms of resistance to these targeted therapies, the patients’ responses vary. These resistances remain a major obstacle in treatment and overcoming them has become a key emphasis of current therapeutic strategies. Intrinsic and acquired resistance often lead to reactivation of downstream signaling pathways, mainly the RAS-RAF-MEK-ERK (MAPK pathway) and PI3K-AKT axes. Prior existing mutations in KRAS, NRAS, and BRAF result in primary resistance by constantly activating the signals, irrespective of EGFR inhibition. That said, acquired resistance manifests under therapeutic burden through the process of clonal evolution via KRAS and BRAF alterations, restoring MAPK pathway activity despite EGFR inhibition. In addition to those mutations, tumor cells exploit mechanisms independent of EGFR, such as the pathway bypass, which includes amplification of ERBB family receptors like HER2 (ERBB2) and activation of MET signaling. To overcome these resistances, novel strategies have emerged, which target multiple nodes within the oncogenic networks. Such methods include vertical pathway inhibition, multi-kinase inhibition, liquid-biopsy-guided therapy, and anti-EGFR rechallenge. Reactivation driven by secondary mutation can be prevented by targeting multiple nodes within the MAPK cascade simultaneously, which is referred to as the vertical pathway inhibition. Overall, this review underscores that overcoming therapeutic resistance requires a multidimensional approach that integrates molecular profiling, rational combination therapies, and adaptive treatment. Finally, these advances underscore the shift toward precision oncology, where therapy is tailored to tumor evolution, leading to improved response and patient outcome.

Photodynamic therapy (PDT) is a minimally invasive anticancer modality based on the interaction of a photosensitizer, light of an appropriate wavelength, and molecular oxygen, resulting in reactive oxygen species (ROS)-mediated tumor injury. This review discusses PDT as a mechanism-dependent therapeutic platform and evaluates how photosensitizers, vitamin A, vitamin D, nanotechnology, and combination strategies may influence its efficacy. The article synthesizes mechanistic and translational evidence concerning photosensitizer activation, ROS generation, tumor cell death, vascular shutdown, immunogenic cell death, and clinically relevant PDT applications. Particular attention is given to the divergent roles of vitamin A and vitamin D. Mechanistic and limited experimental evidence indicates that the effects of vitamin A-related compounds on PDT are heterogeneous and context-dependent. Selected compounds may attenuate PDT through antioxidant or cytoprotective mechanisms, whereas enhancement has also been reported for specific retinoid–photosensitizer combinations; however, clinical evidence remains limited. In contrast, vitamin D may enhance ALA/MAL-PDT by increasing intracellular protoporphyrin IX accumulation through modulation of the heme biosynthetic pathway, especially in non-melanoma skin cancer contexts. Nanocarriers, targeted photosensitizers, oxygen-modulating platforms, chemotherapy, and immunotherapy may further improve PDT when selected according to mechanistic compatibility. Overall, PDT combination design should be guided by whether adjunctive agents support or undermine photosensitizer accumulation, oxygen availability, ROS-mediated cytotoxicity, and immune activation.

Vitamin D comprises a group of fat-soluble secosteroids traditionally associated with animal physiology, calcium-phosphate homeostasis, and skeletal metabolism. However, vitamin D and related compounds have also been reported in taxonomically distinct non-animal systems, including fungi, microalgae, other algae, phytoplankton, and higher plants, although the strength of evidence differs substantially among these groups. This review synthesizes current knowledge on the occurrence, structural chemistry, UV-B-driven photochemical mechanisms, environmental determinants, analytical challenges, and biofortification potential of vitamin D formation in photosynthetic organisms and fungi. Vitamin D synthesis is initiated by UV-B radiation, primarily within the 290–315 nm range, which converts sterol precursors such as 7-dehydrocholesterol and ergosterol into previtamin D intermediates and is followed by thermal isomerization to the corresponding vitamin D forms. Continued irradiation may additionally generate lumisterol, tachysterol, and other photoproducts, thereby limiting net vitamin D accumulation. This non-enzymatic mechanism supports the interpretation that vitamin D formation can occur outside vertebrates when an appropriate 5,7-diene sterol precursor is accessible to a sufficient UV-B dose. In photosynthetic organisms and fungal matrices, net vitamin D accumulation is constrained by the spectral dose of UV-B, environmental exposure, tissue architecture, sterol localization, oxygen availability, antioxidant capacity, and ROS-mediated degradation. Studies of microalgae and phytoplankton, including reports concerning Emiliania huxleyi, suggest the occurrence or UV-B-dependent formation of both vitamin D₂ and vitamin D₃. However, these findings require evaluation according to the analytical method, use of authentic standards, experimental conditions, and confidence of compound identification. In fungi, the UV-B-induced conversion of abundant ergosterol to vitamin D₂ is well established. Microalgae represent a developing source of vitamin D₂ and vitamin D₃, whereas evidence for nutritionally relevant vitamin D accumulation in higher plants remains limited and heterogeneous. Although higher plants contain diverse phytosterols, the formation of vitamin D₄, vitamin D₅, or related analogues requires appropriate photoreactive 5,7-diene precursors and should not be inferred directly from the presence of common phytosterols such as β-sitosterol. Analytical detection remains challenging because of low concentrations, complex lipophilic matrices, and structural similarity among secosteroids and photoproducts; therefore, reliable identification requires validated analytical procedures. LC-MS/MS provides high sensitivity and selectivity but should be supported by authentic standards, preferably isotope-labelled internal standards, retention-time agreement, quantitative and qualifying ions, matrix-recovery assessment, limits of detection and quantification, and evaluation of ion suppression. Structurally similar analogues and photoproducts may additionally require orthogonal confirmation. Nutritionally, post-harvest UV-B enrichment of edible mushrooms is currently the best-validated strategy for increasing non-animal vitamin D₂ content. Microalgae constitute a developing platform for vitamin D₂ and vitamin D₃ production, whereas biofortification of higher plants remains experimental.