Publications

Abstract

Abstract

Extracellular vesicles (EVs) hold great potential for delivering cancer therapy drugs. However, limited efficiency and sophisticated drug encapsulation procedures have hindered their effectiveness. Herein, β-D-glucose is modified with the synthesized photosensitizer (1-(4-carboxybutyl)-4-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5] thiadiazol-4-yl)pyridin-1-ium, named TB) via amide bond to form a glucose-conjugated photosensitizer, referred to as TBG, which is further utilized as a metabolic substrate for cancer cells. Through simple co-incubation with TBG, cancer cells directly generate TBG-engineered EVs in situ via a metabolism-driven process, in which glucose transporters play a critical role. Notably, a higher yield of engineered EVs is observed in TBG-treated cells compared to the TB-treated group. This enhancement could be attributed to increased glucose transporter activity and adenosine triphosphate (ATP) synthesis, highlighting the significance of glucose-modified chemicals. Remarkably, this metabolism-driven strategy has been successfully validated across three cell lines, highlighting its versatility and broad applicability. The extracted TBG-EVs maintain a strong targeting ability toward cancer cells and demonstrate enhanced efficacy in photodynamic therapy for tumor ablation. The study offers an alternative strategy to efficiently produce cargo-loading EVs via direct biological metabolism.

Full Article: https://doi.org/10.1002/adma.202505726

Abstract

Digestive system cancers—including gastric, liver, colorectal, esophageal, and pancreatic malignancies—remain leading causes of cancer death, with treatment resistance posing major challenges in advanced disease. Patient-derived cancer organoids (PDCOs), 3D mini-tumors grown from patient biopsies, have revolutionized personalized oncology by faithfully replicating tumor biology and enabling predictive drug testing for chemotherapy, radiotherapy, targeted therapy, and immunotherapy. While demonstrating good predictive accuracy, current limitations include incomplete tumor microenvironments, variable establishment rates, and lengthy processing times. Emerging technologies like AI, organ-on-chip systems, and 3D bioprinting are addressing these challenges, while clinical trials explore applications in neoadjuvant therapy and real-time treatment guidance. This Review highlights key advances in PDCO technology and its transformative potential for treatment decision-making in digestive system cancers, bridging laboratory research with clinical care to enable truly personalized therapeutic strategies tailored to individual tumor biology.

Full Article: https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-025-02429-0

Abstract

Brain cancer remains among the most lethal malignancies worldwide, with approximately 321,476 new cases and 248,305 deaths reported globally in 2022. The treatment of malignant brain tumors presents substantial clinical challenges, primarily due to their resistance to standard therapeutic approaches. Despite decades of intensive research, effective treatment strategies for brain cancer are still lacking. Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, regulate a broad range of physiological processes including metabolism, immunity, stress response, reproduction, and cellular differentiation. Increasing evidence highlights the involvement of NRs in oncogenesis, with several members demonstrating altered expression and function in brain tumors. Aberrations in NR signaling, encompassing receptors such as androgen receptors, estrogen receptors, estrogen-related receptors, glucocorticoid receptors, NR subfamily 4 group A, NR subfamily 1 group D member 2, NR subfamily 5 group A member 2, NR subfamily 2 group C member 2, liver X receptors, peroxisome-proliferator activated receptors, progesterone receptors, retinoic acid receptors, NR subfamily 2 group E member 1, thyroid hormone receptors, vitamin D receptors, and retinoid X receptors, have been implicated in promoting hallmark malignant phenotypes, including enhanced survival, proliferation, invasion, migration, metastasis, and resistance to therapy. This review aims to explore the roles of key NRs in brain cancer, with an emphasis on their prognostic significance, and to evaluate the therapeutic potential of targeting these receptors using selective agonists or antagonists.

Abstract

Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers within tumors and the immunological camouflage used by cancer cells further complicate treatment efficacy. To overcome these hurdles, ongoing research explores the synergistic potential of combining CAR-T cell therapy with cancer vaccines and other therapeutic strategies such as checkpoint inhibitors and cytokine therapy. This review describes the various immunotherapeutic approaches targeting leukemia, emphasizing the roles and interplay of cancer vaccines and CAR-T cell therapy. In addition, by discussing how these therapies individually and collectively contribute to tumor regression, this article aims to highlight innovative treatment paradigms that could enhance clinical outcomes for leukemia patients. This integrative approach promises to pave the way for more effective and durable treatment strategies in the oncology field. These combined immunotherapeutic strategies hold great promise for achieving more complete and lasting remissions in leukemia patients. Future research should prioritize optimizing treatment sequencing, personalizing therapeutic combinations based on individual patient and tumor characteristics, and developing novel strategies to enhance T cell persistence and function within the tumor microenvironment. Ultimately, these efforts will advance the development of more effective and less toxic immunotherapeutic interventions, offering new hope for patients battling this challenging disease.

Full Article: https://doi.org/10.1186/s40164-025-00662-3

Abstract

The carcinogenesis and drug resistance can be accelerated by TGF-β, primarily by enhancing epithelial-mesenchymal transition (EMT). This review examines the complex mechanisms by which TGF-β drives EMT across different tumors, highlighting its function in increasing cellular plasticity, promoting metastasis, and contributing to therapy resistance. TGF-β activates both canonical Smad-dependent and non-canonical signaling, leading to profound changes in cell morphology, motility, and stemness. This review highlights recent discoveries on how TGF-β regulates cancer stem cells and contributes to drug resistance, including resistance to both conventional chemotherapy and targeted treatments. In addition, it examines the intricate interaction between TGF-β and the key molecular pathways controlling EMT, such as PI3K/AKT, MAPK, and epigenetic regulators. It also examines potential therapeutic approaches aimed at TGF-β-induced EMT, emphasizing promising preclinical results from novel compounds and combination therapies—including natural products, small-molecule inhibitors, and epigenetic regulators—that interfere with TGF-β receptor activation or downstream signaling pathways. Understanding these complex interactions provides valuable insights for developing more effective cancer therapies. The review concludes by identifying key research gaps as well as suggesting future directions for investigating TGF-β’s role in cancer biology and treatment resistance.

Full Article: https://doi.org/10.1016/j.cytogfr.2025.05.004

Abstract

Autophagy is a highly regulated, evolutionarily conserved process of self-digestion controlled by autophagy-related (ATG) genes. It involves the lysosomal degradation of cargoes, including cytoplasmic organelles, misfolded proteins, and toxic aggregates, to enrich cellular nutrient pools and reduce oxidative stress. In normal cells, basal autophagy occurs to maintain cellular homeostasis, which changes during tumor initiation, progression, and malignant transformation. The alteration in autophagy in cancer remains unclear and under-explored. Research indicates that genetic regulations, such as gene mutations, gene polymorphisms, or epigenetic modifications, including DNA methylation, histone modification, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), regulate ATGs, orchestrating the fluctuating nature of autophagy in cancer. Many studies describe the paradoxical role of autophagy in cancer, portraying it as a double-edged sword depending on the context, oscillating between promoting cell survival and inducing cell death-the dual roles in preventing tumor initiation and supporting tumor progression place autophagy at the centre of controversy. Recent findings suggest that autophagy is regulated at the intrinsic cellular level and within the tumor microenvironment. Thus, identifying the molecules, mediators, and mechanisms associated with the regulation of autophagy during tumor development, maintenance, therapy resistance, and dormancy could open new research avenues to enhance the efficacy of cancer therapeutics. Furthermore, this review encompasses preclinical studies and clinical trials, highlighting the effectiveness of modulating autophagy in cancer therapy.