Epigenetic dysregulation can significantly trigger the onset and progression of various diseases, epigenetic therapy is a new treatment strategy by changing DNA methylation, histone modification, N6-methyladenosine, chromatin modification and other epigenetic modifications to regulate gene expression levels for therapeutic purposes. However, small-molecule epigenetic drugs face challenges in disease treatment, such as lack of selectivity, limited therapeutic efficacy, and insufficient safety. Nanomedicine delivery systems offer significant advantages in addressing these issues by enhancing drug targeting, improving bioavailability, and reducing nonspecific distribution. This help minimize side effects while increasing both therapeutic effectiveness and safety of epigenetic drugs. In this review, we focus on the mechanism and role of epigenetic regulatory factors in diseases, as well as the challenges faced by small molecule inhibitors in treatment strategies, especially the research advancements in epigenetic drug delivery systems, review and discuss the therapeutic potential and challenges of using nanotechnology to develop epigenetic drug delivery systems.

Gastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.

Our study aimed to analyze the reported cardiovascular AEs (CVAEs) associated with approved bispecific T-cell engagers (BiTEs) for multiple myeloma (MM), providing insights that could guide safer clinical use of BiTEs. Data were obtained from the FDA Adverse Event Reporting System (FAERS) database for the period from the fourth quarter of 2022 to the first quarter of 2024. A total of 1336 adverse events were reported, of which 112 were CVAEs, accounting for 8.4%. Reporting odds ratio (ROR) and information components (ICs) were extracted from the disproportionality analysis. At standardized MedDRA querie (SMQ) level, arrhythmias (n = 41, ROR025 = 1.49), noninfectious myocarditis/pericarditis (n = 184, ROR025 = 3.11), cardiomyopathy (n = 33, ROR025 = 1.52), shock (n = 23, ROR025 = 4.13) and cardiac failure (n = 16, ROR025 = 1.17) exhibited the positive signal strengths in ROR. And logistic regression analysis reveals that critical risk factors for BiTE-associated CVAEs include older age, male sex, weight loss, cytokine release syndrome, and respiratory failure. In the time-to-onset analysis, majority of CVAEs occurred within the first month (60.9%) and had early-failure type characteristics. It also should be emphasized that CVAEs were commonly associated with serious outcomes, with the most frequently reported being death (34%) Findings above suggest BiTE therapy in MM patients is significantly associated with an increased risk of CVAEs in clinic, and those who develop CVAEs have poorer prognosis. The study may provide important evidence for the precise management and mitigation of cardiovascular risks during BiTE therapy in MM patients, ensuring better clinical outcomes.

Immune checkpoint inhibitors (ICIs) have emerged as a major milestone in cancer immunotherapy. However, their clinical application is limited by significant inter-individual differences in efficacy, the development of resistance, and immune-related adverse events (irAEs). Prodrugs are specially designed to be activated within the tumor microenvironment and release their active components. The concept of prodrugs offers a novel approach to addressing these challenges. This targeted activation not only boosts the effectiveness of ICIs but also minimizes systemic toxicity. This review outlines the biological basis of immune checkpoints and the approved inhibitors targeting them. In addition, it presents the latest research on prodrug designs targeting various immune checkpoints, including PD-1/PD-L1, CTLA-4, LAG-3, IDO, and the CD47/CD24 axis. The mechanisms of action of these prodrugs are detailed, highlighting how they can be activated in the tumor microenvironment to exert their therapeutic effects. Additionally, the review discusses issues related to ICIs drug stability and controlled release, as well as the challenges and prospects in this field. Despite the challenges in prodrug design, innovative nanotechnologies and combination therapeutic strategies hold promise for more effective cancer immunotherapy.

Background: Breast cancer (BC) is one of the most common cancers worldwide. The inevitability of drug resistance to initial anti-HER-2 therapy necessitates the emergence of second-line anti-HER-2 drugs which exhibit a promising outlook. Consequently, it is imperative to appraise their efficacy through network meta-analysis and ascertain their comparative cost-effectiveness.Methods: The data used in our analysis were acquired from patients enrolled in the EMILIA, DESTINY-Breast03, and PHOEBE phase III randomized clinical trials. A partitioned survival model was used for patients diagnosed with HER-2-positive metastatic Breast cancer. The model was crafted with a time horizon of 10 years, operating on a 21-day cycle and incorporating a 5% discount rate for both costs and outcomes. The willingness-to-pay threshold was set at $36,058.06 per quality-adjusted life year (QALY). The impact of parameter uncertainty on the findings was assessed using a one-way deterministic sensitivity analysis and probability sensitivity analysis.Findings: Within the model encompassing 1782 patients, the utilization of pyrotinib plus capecitabine (PC) treatment yielded an additional 0.70 QALY in comparison to T-DM1, resulting in an incremental cost-effectiveness ratio (ICER) of $31,121.53 per QALY gained. Similarly, the administration of T-DXd treatment led to an additional 0.80 QALY compared to T-DM1, resulting in an ICER of $153,950.19 per QALY gained. The PC strategies are considered more cost-effective than T-DM1 when the WTP threshold is set at $36,058.06 per QALY. However, this method is not cost effective for T-DXd. The probability of the PC strategies being cost-effective was 62%, whereas the probability of T-DXd was 0% when compared to T-DM1.Conclusion: PC is a cost-effective therapy for patients afflicted with HER-2-positive metastatic BC compared to T-DM1 from the perspective of China at a WTP threshold of $36,058.06 per QALY. Nevertheless, T-DXd is not as cost-effective as T-DM1, considering its current medication pricing. Therefore, reducing the cost of T-DXd could improve its overall cost-effectiveness.

Acute myelogenous leukemia (AML) is a common malignancy and is supposed to have the ability to escape host immune surveillance. The present study aimed to identify key genes in AML that may affect tumor immunity and to provide prognosis biomarkers of AML. The Cancer Genome Atlas (TCGA) dataset was screened for transcription factors (TFs) involved in immunity and influencing survival, combining Gene Expression Omnibus (GEO) data to validate the impact on patient survival. A prognostic signature was established using four transcription factors, and these genes play an important role in the immune system, with higher regulatory T cell (Treg) scores in high-risk patients compared with the low-risk group. Analysis of individual genes showed that STAT4 and Treg are closely related, which may be due to STAT4 transcribing related genes that affect immunity. STAT4 expression was positively correlated with the proportion of abnormal cells and promoted AML recurrence as verified by AML clinical patient samples. In addition, silencing of STAT4 significantly slowed down the proliferation capacity of HL60 cells. In conclusion, these findings suggest that STAT4 may be a potential biomarker for AML prognosis. As a key gene affecting the prognosis of AML patients, STAT4 has the potential to be a candidate diagnostic and prognostic biomarker for AML.