bims-metorg 2025-12-28 papers

Issue of 2025–12–28
two papers selected by
Bruna Martins Garcia, CABIMER

Med Oncol. 2025 Dec 26. 43(2): 93

"Exosomal blueprint of lung-tropic metastasis: molecular signatures, microenvironmental conditioning, and translational implications in cancer".

Noura A A Ebrahim, Thoraya A Farghaly, Soliman M A Soliman.

Exosomes are increasingly recognized as central regulators of organ-specific metastasis, and this review concentrates on their contribution to lung-directed dissemination. Yet, a detailed and integrative synthesis of how exosomes contribute to lung-directed metastatic spread-and what these mechanisms mean for clinical translation-remains largely absent from the current literature. Extracellular vesicles (EVs), particularly exosomes measuring 30-150 nm, are nanoscale, lipid bilayer-enclosed structures secreted by nearly all cell types. In cancer, tumor-derived exosomes act as potent mediators of intercellular signaling, enabling metastatic spread by modulating inflammation, angiogenesis, extracellular matrix dynamics, and immune evasion. Their molecular cargo, especially integrin profiles, plays a decisive role in determining metastatic tropism: integrins α6β4 and α6β1 are strongly associated with pulmonary colonization, while αvβ5 directs metastasis toward the liver. In malignancies such as breast, colorectal, melanoma, and pancreatic cancer, exosomal proteins and RNAs remodel the lung microenvironment, enhancing vascular permeability and attracting stromal and immune components that establish a receptive pre-metastatic niche. Clinically, exosomes are emerging as powerful liquid biopsy biomarkers and as promising platforms for targeted drug delivery. Advances in EV bioengineering now permit tailoring of surface molecules and cargo to improve pulmonary selectivity, for instance, supporting selective delivery of therapeutic payloads to pulmonary tumors or altering immune dynamics within the lung microenvironment, while omics-based and imaging technologies support detailed profiling and tracking. Early clinical trials of exosome-derived vaccines and therapeutic carriers have demonstrated feasibility and safety, although no EV-based therapy has yet achieved regulatory approval. This review integrates mechanistic insights, niche biology, and translational advances to highlight the unique role of exosomes in lung-specific metastasis and their potential as diagnostic and therapeutic tools in precision oncology.

Keywords: Cancer biomarkers; EV engineering; Exosomes; Extracellular vesicles; Integrins; Liquid biopsy; Lung tropism; Metastasis; Organotropism; Pre-metastatic niche; Targeted drug delivery

DOI: https://doi.org/10.1007/s12032-025-03217-y

Front Oncol. 2025 ;15 1712576

Metabolism of glioblastoma: a review of metabolic adaptations and metabolic therapeutic interventions.

James Chung, Jawad Saad, Ahmad Kafri, Julien Rossignol, Maxwell Verbrugge, Jesse Bakke.

Glioblastoma (GBM) is the most common and aggressive primary malignancy of the central nervous system, marked by profound metabolic reprogramming that promotes growth, invasion, and therapeutic resistance. This review examines metabolic adaptations that sustain GBM progression and summarizes current and emerging strategies that target these pathways. GBM cells display increased aerobic glycolysis, glutaminolysis, lipid and cholesterol synthesis, and mitochondrial remodeling. These processes are regulated by oncogenic alterations such as EGFR amplification, PTEN loss, and HIF-1α stabilization, which allow tumor cells to thrive in hypoxic and nutrient-poor environments. Accumulation of lactate further supports metabolic flexibility and promotes an immunosuppressive microenvironment. Recent studies have focused on exploiting these metabolic vulnerabilities through dietary, pharmacologic, and oxygen-modulating interventions. The ketogenic diet has been explored as an adjuvant therapy to reduce glucose availability and enhance treatment sensitivity. Pharmacologic approaches include inhibition of key metabolic enzymes such as hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase, and glutaminase. Additional strategies aim to disrupt mitochondrial function through VDAC1 blockade or to reduce tumor hypoxia using hypoxia-activated prodrugs, hyperbaric oxygen therapy, and oxygen-transporting agents. Preclinical findings suggest these approaches can suppress tumor proliferation and improve responsiveness to radiation and chemotherapy, although clinical evidence remains limited. Combining metabolic interventions with standard therapies may help overcome GBM's intrinsic resistance and metabolic plasticity. Overall, the review highlights metabolism as a key determinant of GBM pathophysiology and a promising target for therapeutic innovation, emphasizing the importance of continued translational research to identify and exploit context-specific metabolic vulnerabilities in this highly lethal disease.

Keywords: brain cancer; cancer; cancer signaling; glioblastoma; metabolic therapeutics; metabolism

DOI: https://doi.org/10.3389/fonc.2025.1712576