Epigenetic regulation is a fundamental mechanism controlling gene expression and cellular function, primarily mediated through reversible modifications such as DNA methylation, histone acetylation, and chromatin remodeling. Dysregulation of critical epigenetic enzymes, including histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and bromodomain and extraterminal domain (BET) proteins, has been closely associated with tumor initiation, progression, metastasis, immune evasion, and resistance to conventional therapies. Targeting these epigenetic regulators with small-molecule inhibitors or degraders has emerged as a promising therapeutic strategy, capable of reprogramming aberrant transcriptional networks and reshaping the tumor microenvironment. Beyond direct cytotoxic effects, epigenetic drugs have demonstrated the ability to enhance antitumor immunity by restoring antigen presentation, promoting immunogenic cell death, modulating cytokine profiles, and reversing local immune suppression. Recent preclinical and clinical studies have highlighted the potential of combining epigenetic therapies with immune checkpoint inhibitors to achieve synergistic antitumor responses and overcome resistance mechanisms. This review provides a comprehensive summary of the mechanisms of action, pharmacological characteristics, and clinical applications of epigenetic drugs, with a focus on innovative combination strategies and ongoing translational advancements. We also discuss future directions, emphasizing the need to improve drug specificity, minimize off-target effects, integrate personalized immunotherapeutic approaches, and identify predictive biomarkers to optimize patient selection and clinical outcomes. Overall, epigenetic therapy represents a versatile and evolving avenue for precision oncology with broad implications for tumor control and immunomodulation.

Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Aberrant regulation of DNA methylation in promoters of tumor suppressor genes or proto-oncogenes is one of the fundamental processes driving the initiation and progression of CRC. Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and function in many important biological processes related to tumorigenesis. Herein, we detected abnormal hypermethylation of the ZNF334 gene in CRC tissues compared with normal tissues, and this modification downregulated the expression of ZNF334. Furthermore, ten-eleven translocation 1 (TET1) was identified to be involved in regulating the methylation level of ZNF334. Next, a dCas9-multiGCN4/scFv-TET1CD-sgZNF334-targeted demethylation system was constructed to reverse the expression of ZNF334 through sgRNA targeting the ZNF334 promoter. Both in vitro and in vivo experiments demonstrated the targeted demethylation system upregulated ZNF334 expression and inhibited CRC growth. Collectively, targeted DNA demethylation of the ZNF334 promoter sheds light on the precise treatment of CRC.

Quercetin reverses the expression of abnormal genes by regulating DNA methylation, and is an important regulator of gene transcription in tumorigenesis. The use of nanoscale delivery of quercetin increases its bioavailability in cancer therapy.

Metal–polyphenol networks (MPNs), a novel class of nano-biomaterials, have recently emerged as promising candidates for tumor diagnosis and therapy due to their unique chemical tunability, excellent biocompatibility, and synergistic multifunctionality. Notably, MPNs can be synthesized via one-step or multi-step approaches, allowing precise control over their morphology, size, and drug-loading capacity. The versatility of MPNs is further demonstrated by their ability to integrate multiple therapeutic modalities, including chemotherapy, photothermal therapy, photodynamic therapy, and chemical dynamic therapy. Furthermore, through surface modification with targeted molecules, MPNs enable tumor-specific targeting while facilitating real-time therapeutic monitoring via multimodal imaging. Additionally, MPNs exhibit excellent biocompatibility and superior biodegradability, making them highly suitable for biomedical applications. This review systematically explores MPN synthesis strategies and physicochemical properties. It then comprehensively analyzes MPN-based biomaterials and their tumor therapeutic mechanisms. Furthermore, we evaluate the challenges in MPN clinical translation and propose future perspectives for precise tumor treatment using MPN-based platforms. Ultimately, this review highlights the transformative potential of MPNs in advancing tumor theranostics and lays the foundation for their future clinical applications.