Medical Oncology最新文献

Endocrine tumors are hormone-secreting tumors that pose significant challenges for diagnosis and treatment due to their complex biological processes, delayed detection, and poor response to existing therapies. Despite advancements in imaging, surgery, and medicine, tumor heterogeneity, substantial barriers, and systemic toxicity hinder therapeutic success. A novel approach utilizing nanotechnology presents theranostics capabilities for various applications, enhances bioavailability, and ensures precise drug delivery. Engineered nanoparticles (NPs), including lipid-based, polymeric, and inorganic nanocarriers, enable targeted therapy through active targeting (ligand-receptor interactions) or passive accumulation (increased permeability and retention). These nanotechnologies address drug resistance and rapid clearance, delivering treatments directly to tumors while minimizing adverse effects on healthy cells. NPs that mimic biological processes or respond to external stimuli can adapt to the evolving tumor microenvironment. This review focuses on NP-based therapy for endocrine cancer, discussing their mechanisms of action, targeted approaches, and diagnostic and therapeutic applications. The limitations of current therapies and the future prospects of NP-based therapies are explored.

Fungi are a vital component of the gastrointestinal microbiota and are increasingly recognized for their critical roles in the initiation, progression, and therapeutic response of digestive tract cancers. Accumulating evidence indicates that specific fungal species contribute to the pathogenesis of various gastrointestinal malignancies-including oral, esophageal, gastric, and colorectal cancers-by promoting chronic inflammation, inducing host DNA damage, and modulating immune responses. Moreover, fungal-bacterial interactions can indirectly influence tumorigenesis by disrupting microbial community homeostasis and altering the functional landscape of the gut microbiome. In this review, we systematically synthesize current evidence from human cohort studies, preclinical models, and multi-omics analyses to delineate mycobiome-cancer associations, elucidate underlying mechanisms, and evaluate emerging diagnostic and therapeutic strategies. Together, these insights position the mycobiome not merely as a bystander but as an active contributor to gastrointestinal carcinogenesis-offering novel opportunities for early detection, risk stratification, and microbiome-targeted interventions in cancer prevention and therapy.

This letter commends the recent study by Abdelkarim et al. on the pro-apoptotic effects of an Allium sativum (garlic) extract in acute myeloid leukemia (AML). While acknowledging the significance of their ex vivo findings on primary patient cells, we propose several key considerations to strengthen the translational potential of this research. Firstly, we emphasize the need for standardized phytochemical characterization of the complex extract to ensure reproducibility. Additionally, we suggest expanding the mechanistic investigation to include the extrinsic apoptosis pathway and direct measurement of reactive oxygen species. Furthermore, we discuss strategies to enhance the targeting of resistant leukemia stem cell populations, such as prolonged exposure or combination therapy with venetoclax. Finally, we advocate for in vivo validation using patient-derived xenograft models to evaluate efficacy within a physiologically relevant microenvironment. Addressing these points will be crucial for harnessing the full potential of Allium sativum as a complementary therapy in AML.

Exosomes are among the various secreted vesicles which play a pivotal role in tumor growth and progression. In fact, tumor-derived exosomes are considered to be an excellent reservoir of oncogenic factors which govern the metastatic potential of cancer cells. Previously, we observed systemic damage within the lymphoma-bearing host and established the immunomodulatory effect of lymphoma-derived factors/ascites on macrophages. However, whether this host-tumor interaction involves exosomes or not remains unclear. In view of this, we aimed to explore the proteomics landscape of tumor-derived exosomes to unravel their possible involvement in governing lymphoma-induced pathogenicity. Interestingly, we observed significant increase in exosome abundance in blood and tissues of lymphoma-bearing hosts. Comprehensive proteome profile of exosomes revealed a distinct set of tumor-associated proteins, such as metalloproteinases (MMPs) and myeloperoxidase, which might be mediating tissue degradation within the host. Various exosomal proteins overlapped with known markers of epithelial to mesenchymal transition (EMT) and lymphoma. Functional enrichment analysis of exosomal cargoes revealed their immunomodulatory potential which could alter the activation state of macrophages. In vitro assay confirmed active uptake of these exosomes by macrophages resulting in morphological alterations, increased reactive oxygen species (ROS) production and reduction in LPS-induced nitrite release by inhibiting NOS2 expression. Conclusively, exosome abundance in blood and tissues highlight their possible involvement in mediating systemic alterations in lymphoma-bearing hosts. This study gives the first evidence of MMP-8 within the exosomes suggesting a novel pathway for its contribution to tissue damage in cancer condition. The study underscores the possible link for exosome-macrophage crosstalk to promote systemic immunomodulation in lymphoma. Our results give key insight into exosome profiling and illustrate the presence of invasive and immunomodulatory proteins which might be used as diagnostic or prognostic markers and could serve as an important target in therapeutic intervention in cancer.

Tumor hypoxia poses a major challenge in tumor therapy. Many strategies have been explored to alleviate tumor hypoxic microenvironment to improve the efficacy of tumor therapy. Ultrasound-stimulated microbubbles cavitation (USMC) was proved to improve tumor perfusion, and thus to alleviate tumor hypoxia. The synergistic role of USMC in tumor therapy has been identified by several preclinical and clinical studies. The effect of USMC on improving tumor perfusion is influenced by many factors, and the stability and reproducibility of this effect in long-term tumor treatment remain to be explored. In this study, we established rabbit VX2 tumor model. Fifteen tumor-bearing rabbits were enrolled to compare the effects of USMC with two different mechanical indexes (MIs). The results of contrast-enhanced ultrasound (CEUS) imaging showed that USMC with MI of 0.25 could improve the tumor perfusion better compared with MI 0.40. Then we conducted repeated USMC treatments on tumor-bearing rabbits once a week for six weeks. The results of CEUS showed that USMC with appropriate parameters could always enhance the tumor perfusion although the tumor had developed. Transmission electron microscopy revealed that tumors received multiple USMC treatments had more integral vascular structures compared with the control. Immunofluorescence staining showed that tumors received multiple USMC treatments had higher overlap coefficient of CD31 and intercellular cell adhesion molecule-1, indicating the normalization of tumor vasculature. In conclusion, USMC with appropriate parameters has stability and reproducibility in improving tumor perfusion. And multiple USMC treatments could potentially promote tumor vascular normalization, which is beneficial for tumor therapy.

Epigenetic modifications act as crucial controllers of gene expression in nasopharyngeal carcinoma (NPC), with DNA hypermethylation of tumour suppressor genes and alterations in histone modification patterns playing a major role in oncogenesis. EBV-encoded proteins directly modulate host epigenetic machinery, promoting stable silencing of critical genes. Environmental exposures, such as nitrosamines and tobacco smoke, further influence epigenetic risk. Non-coding RNAs, especially miRNAs and lncRNAs, modulate epigenetic regulators and contribute to tumour behaviour. Several epigenetic markers show strong potential as non-invasive diagnostic and prognostic tools. Epigenetic drugs, such as HDAC and DNMT inhibitors, therapeutically show promise in reactivating silenced genes and sensitising tumours to conventional treatments. Epigenomic alterations offer profound insights into NPC pathogenesis and present valuable opportunities for early detection, risk assessment and targeted therapy. With the advances in epigenomic profiling technologies and increasing clinical validation, epigenetic biomarkers and therapeutics may become integral to precision oncology approaches in NPC. Continued interdisciplinary research is essential to fully harness these insights and translate them into improved outcomes for patients. This review presents an in-depth summary of the current understanding regarding epigenomic alterations in NPC, with a focus on their biological significance, diagnostic utility, and therapeutic potential in NPC initiation, progression and treatment.

Oral squamous cell carcinoma (OSCC) is the most prevalent form of head and neck squamous cell carcinoma (HNSCC), characterized by high incidence rates, frequent recurrence and metastasis, and low survival rates. KLHL4, a member of the Kelch-like family proteins, plays a significant role in cancer. However, the role of KLHL4 in OSCC remains largely unexplored. In this study, we first identified the aberrant overexpression of KLHL4 in OSCC tissues through Western blotting and immunohistochemistry. Subsequent experiments, including qPCR, colony formation assays, scratch assays, and transwell invasion and migration assays, demonstrated that knockdown of KLHL4 inhibits OSCC growth, migration and invasion in vitro. Furthermore, through the establishment of subcutaneous xenograft models and lung metastasis models in nude mice, we revealed that KLHL4 knockdown suppresses tumor growth and metastasis in vivo. We also found that KLHL4 knockout inhibited 4NQO-induced OSCC progression. Mechanistically, co-immunoprecipitation confirmed the physical interaction between KLHL4 and EGFR, while rescue experiments using EGF and Afatinib demonstrated the functional dependency of KLHL4 on EGFR pathway activation. Clinical analysis of a 112-case OSCC tissue microarray revealed that high KLHL4 expression correlated significantly with lymph node metastasis and predicted poor patient overall survival, which was independently validated in a public HNSCC cohort. Overall, our research highlights the critical role of KLHL4 in the malignant progression of OSCC through upregulating the EGFR signaling pathway, indicating its potential as a therapeutic target for OSCC treatment.

Adeno-associated virus (AAV) has emerged as a pivotal vector for cancer gene therapy due to its low immunogenicity, non-pathogenicity, and sustained transgene expression capacity. However, the heterogeneity and complexity of the tumor microenvironment (TME) significantly constrain the delivery efficiency and targeting precision of AAV in solid tumors. Dense extracellular matrix, acidic and hypoxic conditions, and immunosuppressive signaling networks collectively impede effective AAV transduction while increasing off-target risks. To overcome these barriers, recent advances have introduced interdisciplinary optimization strategies, including dynamic engineering of AAV capsids, TME-responsive gene expression systems, and biomimetic camouflage technologies to enhance immune evasion and tumor targeting. Furthermore, data-driven AAV engineering, integrating machine learning and high-throughput screening, has significantly accelerated the development of next-generation vectors. This review systematically summarizes intelligent design strategies for TME-responsive AAV vectors and their progress in precision oncology, with a focus on overcoming key delivery barriers to achieve highly efficient and low-toxicity cancer therapy.

Pathologically, primary liver cancer is a heterogeneous, aggressive malignancy and encompasses hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and other rare tumors. This cancer remains the fifth most common malignancy in men and the eighth in women and the fourth leading cause of cancer-related mortality worldwide. Clinically, most liver cancer occurs typically from a background of cirrhosis and chronic inflammation. Liver cancer remains difficult to treat; small-molecule kinase inhibitors such as sorafenib and lenvatinib have only limited clinical benefit. Therefore, an urgent need exists to develop novel drugs for the treatment of liver cancer. Triterpenoids, consisting of six isoprene units, are structurally diverse secondary metabolites and possess versatile biological activities including immunomodulatory and antitumor activities. In this review, we discuss the therapeutic potential of natural triterpenoids in liver cancer, primarily focusing on their possible mechanisms involving induction of cell cycle arrest, initiation of apoptosis, activation of autophagy, stimulation of antitumor immune response, suppression of angiogenesis and metastasis, and enhancement of radio/chemo-sensitivity. We also present the current challenges that impede their translation to clinical practices. We conclude that natural triterpenoids could serve as potential candidates for developing liver cancer therapies, based on the current preclinical evidence. However, their clinical translation requires further validation. Hopefully, the knowledge gained from this review will outline future research directions and identify current research priorities in this field.