Epigenetic alterations are implicated in the early stages of tumorigenesis and are widely recognized as a ubiquitous phenomenon in cancer development. Aberrant epigenetic modifications can alter the expression of target genes, induce heterochromatin formation, and gradually drive normal cells towards immortalized tumor cells with significant consequences. SETDB1 (SET domain bifurcated histone lysine methyltransferase 1), a typical histone me-thyltransferase, promotes the formation of heterochromatin and inhibits the transcription of genes by modifying the methylation of lysine 9 of histone 3. SETDB1 is usually highly ex-pressed in tumors with high copy numbers, accompanied by poor prognosis and low patient survival rates, which is a typical case of abnormal epigenetic modification. We discuss the mechanism of SETDB1 in a variety of cancers and review the epigenetic inhibitors that have been reported in recent years, along with their anti-tumor effects. In addition, we summarize the role of SETDB1 in a variety of diseases and cell functions.

BACKGROUND: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive.
OBJECTIVE: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development.
OBJECTIVE: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma.
METHODS: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape.
RESULTS: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes\' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma.
CONCLUSIONS: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

BACKGROUND: Dysregulated splicing events are a common phenomenon in cancer with the Serine-arginine-rich splicing factor (SRSF) family emerging as pivotal regulators of gene expression, exerting influence over constitutive and alternative splicing processes. Although aberrations in a few SRSF family members have been implicated in various cancers, the comprehensive roles of other family constituents remain underexplored.
METHODS: This study delves into the expression profile of the entire SRSF family (SRSF1-SRSF12) in 23 cancerous cell lines originating from diverse tissues using quantitative Real-Time PCR. Further, the transcript levels of the SRSF family were examined in oral cancer patient samples stratified into Pre-cancer (n = 15), Early cancer (n = 11), Late cancer (n = 14), and adjacent non-tumor tissues (n = 26) as controls. The results were corroborated by a parallel investigation utilizing the transcriptomics data of oral squamous cell carcinoma (OSCC) patients (n = 319) and controls (n = 35) available in The Cancer Genome Atlas (TCGA) database.
RESULTS: Our investigation reveals a notable upregulation in the expression levels of key splicing factors, namely SRSF3, SRSF9, and SRSF10 in all oral cancer cell lines (SCC-4, UM-SCC-84, CAL33, SAS-H1). Conversely, no significant associations between SRSF family members and other cancer cell lines were discerned. Further, the expression profile of the SRSF family in oral cancer patient samples revealed significant upregulation of SRSF1, SRSF3, SRSF7, SRSF9, SRSF10, and SRSF11 in patients with late-stage oral cancer compared to controls. Transcriptomics data from TCGA database demonstrated remarkable upregulation of SRSF1, SRSF4, SRSF9, SRSF10, and SRSF11 in OSCC patients.
CONCLUSIONS: Collectively our results underscore the critical involvement of SRSF family members in the context of oral cancer, highlighting their potential as key players in the altered splicing dynamics associated with cancer progression.

Esophageal cancer (EC) is one of the most fatal cancers all over the world. Sensitive detection modalities for early-stage EC and efficient treatment methods are urgently needed for the improvement of the prognosis of EC. Exosomes are small vesicles for intercellular communication, mediating many biological responses including cancer progression, which are not only promising biomarkers for diagnosis and prognosis but also therapeutic tools for EC. This review provides an overview of the relationships between exosomes and EC progression, as well as the application of exosomes in the diagnosis, prognosis, and treatment of EC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Intramedullary nailing insertion from the proximal-to-distal femur is frequently performed for impending and complete pathological femur fractures due to osteolytic metastases. After nailing through cancer-laden bone, residual chemotherapy- and/or radiation-resistant tumor may progress. Progression of osteolysis risks future nail failure or pathological fractures. This study assesses the incidence of cancer progression following intramedullary nailing in a femur-only cohort and describes a percutaneous rod-retaining salvage technique. A single-institution, retrospective study was conducted to identify adult patients who underwent intramedullary nailing for femoral osteolytic lesions for complete or impending nail failure from 2016 to 2023. Progression was defined as enlargement of the pre-existing lesion and/or appearance of new lesions on radiographs. Surgical outcomes were assessed with a combined pain and functional score. A total of 113 patients (median age 66.8 years (IQR = 16.4); median follow-up 6.0 months (IQR = 14.5)) underwent intramedullary nailing. Sixteen patients (14.2%) exhibited post-nailing cancer progression. Pre- and postoperative radiation and chemotherapy did not decrease the odds of cancer progression. Three patients underwent initial open surgical salvage consisting of proximal femur replacement arthroplasty, and six patients did not receive salvage due to poor surgical candidacy or patient choice. Seven patients (median follow-up 10.7 months (IQR = 12.9)) received percutaneous salvage. In this group, pain and functional scores improved by 4.0 points (p = 0.0078) at two-week postoperative follow-up and 2.0 points (p = 0.0312) at the most recent follow-up (mean follow-up 13.0 ± 9.4 months). All three nonambulatory patients became ambulatory, and six patients were able to ambulate independently without walking aids. No major complications were reported 30 days postoperatively. Progression of femoral osteolytic metastases may occur following intramedullary nailing. Continued monitoring of the entire femur is needed to maintain improved functional status and to prevent catastrophic progression of pre-existing lesions or appearance of new lesions. In patients with more proximal metastases only, the customary practice of bringing a long nail from the proximal femur to distal metaphysis should be reconsidered. Furthermore, there is concern of mechanical transport of cancer cells during guide wire insertion, reaming, and rod insertion through cancer laden bone to cancer free distal bone.

Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression. In response to inflammatory stimuli, neutrophils become activated, releasing neutrophils extracellular traps (NETs) for the capture and eradication of pathogens, a phenomenon termed NETosis. With a deeper understanding of NETs, there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies, especially concerning tumor reactions to chemotherapy, radiation therapy (RT), and immunotherapy. This review summarizes the roles of NETs in the tumor microenvironment (TME) and their mechanisms of neutrophil involvement in the host defense. Additionally, it elucidates the mechanisms through which NETs promote tumor progression and their role in cancer treatment resistance, highlighting their potential as promising therapeutic targets in cancer treatment and their clinical applicability.

By the beginning of the year 2021, the estimated number of new cancer cases worldwide was about 19.3 million and there were 10.0 million cancer-related deaths. Cancer is one of the deadliest diseases worldwide that can be attributed to genetic and environmental factors, including nutrition. The good nutrition concept focuses on the dietary requirements to sustain life. There is a substantial amount of evidence suggesting that a healthy diet can modulate cancer risk, particularly the risk of colorectal and breast cancers. Many studies have evaluated the correlation between our diet and the risk of cancer development, prevention, and treatment. The effect of diet on cancer development is likely to happen through intertwining mechanisms including inflammation and immune responses. For instance, a greater intake of red and processed meat along with low consumption of fruits and vegetables has been associated with increased levels of inflammatory biomarkers that are implicated in cancer development. On the other hand, the consumption of phytosterols, vitamins, and minerals, which exert antioxidant and anti-inflammatory roles have been linked to lower cancer risk, or even its occurrence prevention. In this book, we aim to summarize the current knowledge on the role of nutrition in cancer to provide the best scientific advice in this regard.

RNA modifications play a crucial role in cancer development, profoundly influencing various stages of the RNA lifecycle. These stages encompass nuclear processing, nuclear export, splicing, and translation in the cytoplasm. Among RNA modifications, RNA ac4C modification, also known as N4-acetylcytidine, stands out for its unique role in acetylation processes. Specific proteins regulate RNA ac4C modification, maintaining the dynamic and reversible nature of these changes. This review explores the molecular mechanisms and biological functions of RNA ac4C modification. It examines the intricate ways in which RNA ac4C modification influences the pathogenesis and progression of cancer. Additionally, the review provides an integrated overview of the current methodologies for detecting RNA ac4C modification. Exploring the potential applications of manipulating this modification suggests avenues for novel therapeutic strategies, potentially leading to more effective cancer treatments in the future.

Angiogenesis is recognized as a hallmark of cancer, and vascular endothelial growth factor (VEGF) is a key regulator of the angiogenic process and is related to cancer progression. Anti-VEGF therapy has been tried but with limited success and without useful stratification for angiogenesis markers. Further, the landscape of VEGF single nucleotide polymorphisms (SNPs) in breast cancer and their clinical relevance is not well studied, and their relation to tissue-based angiogenesis markers has not been explored. Here, we studied a selection of VEGFA SNPs in nontumor lymph nodes from a population-based breast cancer cohort (n = 544), and their relation to clinicopathologic variables, vascular tissue metrics, and breast cancer-specific survival. Two of the SNP candidates (rs833068GA genotype and rs25648CC genotype) showed associations with angiogenesis tissue markers, and the VEGFA rs833068GA genotype was associated with breast cancer-specific survival among ER-negative cases. We also found trends of association between the rs699947CA genotype and large tumor diameter and ER-negative tumors, and between the rs3025039CC genotype and large tumor diameter. Our findings indicate some associations between certain VEGF SNPs, in particular the rs833068GA genotype, and both vascular metrics and patient survival. These findings and their potential implications need to be validated by independent studies.