Yuan Tian

Chronic inflammation is a fundamental driver of cancer development, linking persistent immune activation to genomic instability, microenvironmental remodeling, and malignant transformation. In inflammation‐associated malignancies such as colitis‐associated cancer (CAC) and metabolic dysfunction–associated fatty liver disease–related hepatocellular carcinoma (MAFLD‐HCC), sustained inflammatory signaling integrates tissue injury with oncogenic pathways to promote tumor initiation and progression. Importantly, these cancers arise through prolonged preneoplastic stages, during which dysregulated immune and inflammatory responses not only drive malignant transformation but also create opportunities for cancer prevention and early disease interception. CAC and MAFLD‐HCC share convergent mechanisms, including IL‐6/STAT3 and NF‐κB activation, cytokine‐driven survival signaling, and cooperation with genetic alterations in APC, KRAS, and TP53. A critical but often underappreciated dimension of this process is the failure of endogenous immunoregulatory systems that normally restrain excessive inflammation. Among these, the negative regulator of immune cells TIPE2 plays an important role in limiting inflammatory signaling, and its reduced activity contributes to the persistence of a tumor‐promoting inflammatory microenvironment that supports both disease initiation and progression. This review synthesizes the shared inflammatory, immunologic, and microenvironmental mechanisms underpinning CAC and MAFLD‐HCC, with a particular emphasis on how impaired immune regulation drives the transition from chronic inflammation to cancer. We further highlight therapeutic and preventive strategies targeting inflammation‐driven pathways, underscoring the dual relevance of immune modulation for cancer prevention in chronic inflammatory disease and for the treatment of established malignancy.

Cells are often under attack from various DNA-damaging agents. Accurate repair is required to protect cells from the genome instability induced by DNA lesions. DNA damage response (DDR) signaling involves sensitizing, transmitting, and repairing different types of damage within chromatin complexes. Chromatin is a highly ordered complex packed with repeating units of nucleosomes and linker DNA sequences. Chromatin structure, gene transcription, and various biological processes are regulated by histone post-translational modifications (PTMs), including acetylation, methylation, phosphorylation, and ubiquitylation. Of these, the involvement of lysine methylation, regulated by numerous lysine methyltransferases and demethylases, in the DDR has been extensively explored. In particular, histone 4 lysine 20 methylation is one of the most essential histone PTMs for biological processes and ensures genome integrity. In this review, we summarize the dynamics and modulations of histone lysine methylation during the DDR. We also comprehensively describe the functions, mechanisms, and regulation of H4K20 methylation and its modifying enzymes in response to DNA damage.