Cancer remains a major global health burden, and therapeutic progress is frequently undermined by acquired drug resistance. A key contributor to drug resistance is the ability of malignant cells to evade programmed cell death (PCD). In this review, we summarize six canonical PCD modalities-apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis-and emphasize their interdependence within a densely connected regulatory network. We highlight how PANoptosis links apoptosis, necroptosis, and pyroptosis, how ferroptosis and cuproptosis converge on shared redox circuitry, and how immunogenic cell death communicates bidirectionally with the tumor microenvironment. Because cancer cells can escape PCD through adaptive rewiring, single-agent interventions are often insufficient. We therefore propose synergistic, multitarget strategies that modulate multiple signaling cascades while engaging alternative death pathways to avert compensatory drug resistance. Finally, we discuss emerging tools-including single-cell omics, AI-assisted modeling, CRISPR screening, and nanoparticle delivery-that enable mechanistic dissection and precision targeting of PCD networks. Future studies should adopt a holistic, context-dependent view of PCD, identify cancer-type-specific biomarkers that could predict drug response in vitro and in vivo, and accelerate translation of rational combination therapies to overcome pharmacological resistance in malignant disorders.

Gene editing and RNA editing technologies are advancing modern medicine by enabling precise manipulation of genetic information at the DNA and RNA levels, respectively. The third‐generation gene editing tools, particularly Clustered regularly interspaced shortpalindromic repeats (CRISPR)/CRISPR‐associated (Cas) system, have transformed genetic disease treatment with high efficiency, precision, and cost effectiveness, while RNA editing, via adenosine deaminase acting on RNA (ADAR) enzymes and CRISPR–Cas13, offers reversible regulation to avoid genomic integration risks. Despite advancements, challenges persist in delivery efficiency, tissue specificity, and long‐term safety, limiting their clinical translation. This review systematically discusses the molecular mechanisms and technological evolution of these tools, focusing on their promising applications in treating nervous system disorders (e.g., Alzheimer's, Parkinson's), immune diseases (e.g., severe combined immunodeficiency, lupus), and cancers. It compares their technical attributes, analyzes ethical and regulatory issues, and highlights synergies between the two technologies. By bridging basic research and clinical translation, this review provides critical insights for advancing precision medicine, reshaping disease diagnosis, prevention, and treatment paradigms.

With an increasing global cancer burden, the regulatory function of the human microbiome and its metabolites in tumor epigenetics has garnered significant interest. Microbial metabolites are not merely passive byproducts but serve as signaling molecules and epigenetic modulators, contributing to tumor progression through multiple overlapping pathways. Short‐chain fatty acids (SCFAs) such as butyrate directly inhibit histone deacetylases to reactivate tumor suppressor genes, while secondary bile acids (BAs) induce gene silencing via DNA methylation remodeling by altering the FXR/TGR5 signaling pathway. Folate and vitamin B12 serve as substrates for DNA and histone methylation through one‐carbon metabolism. A complex bidirectional feedback loop exists between microbial metabolism and tumor epigenetics: reprogramming driven by hypoxia or oncogenes alters metabolite flux, generating molecules such as lactate and succinate that not only remodel chromatin and the tumor microenvironment (TME) but also selectively promote the growth of metabolically adapted microbial species, thereby reinforcing epigenetic dysregulation. Despite growing mechanistic insights, establishing causality and correlating spatiotemporal dynamics and dose responses within the highly heterogeneous TME remain major challenges. Data integration across multi‐omics remains limited by methodological and computational constraints. Resolving these issues will be critical for understanding the microbe–metabolite–epigenetic axis and advancing personalized precision oncology.

The rapid development of DNA- and RNA-editing tools (collectively referred to as gene editing technologies) has caused a paradigm shift in the treatment of human diseases from symptomatic treatment to precision-based medicine. Both DNA-based and RNA-based editing systems, including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–derived technologies and newly developed RNA editing tools, have pushed technological frontiers in terms of editing precision, hierarchical control, and reversibility; they have accumulated a growing body of preclinical and clinical evidence across diverse diseases ranging from inherited disorders to cancer, infectious diseases, and neurodegenerative diseases (ND). This review systematically summarizes the core principles and representative advances of DNA-based genome editing and RNA-based transcriptome editing technologies, comprehensively compares the two categories of technical strategies in terms of therapeutic potential, durability of effects, and risk profiles, and further explores the key challenges for achieving long-term safe and efficient in vivo applications, covering core bottlenecks such as delivery efficiency, tissue specificity, genotoxicity, and immunogenicity. Safety assessment has broadened to include tracking genotoxicity and genomic structural variations, whereas delivery systems and tissue specificity are determinant factors for in vivo therapeutic applications. Through the employment of both permanent and reversible editing strategies with high cargo-writing capacity and low integration risk, combined with programmable delivery systems, the therapeutic potential of hard-to-transfect tissues and complex diseases is anticipated to be broadened, opening new paths for clinical translation.

Wound healing is the dynamic biological process by which an organism restores homeostasis following injury and is characterized by a series of stages resulting in hemostasis, inflammatory response, proliferation, and tissue remodeling. As a consequence, the inflammatory response represents a key early step in this process and plays a central role in clearing necrotic debris and pathogens, as well as inducing reparative pathways. Mild to moderate inflammation induces angiogenesis, fibroblast activation, and extracellular matrix (ECM) remodeling, whereas chronic or excessive inflammation causes tissue damage, fibrosis, and chronic non-healing wounds. The current review systematically illustrates the contribution and dynamics of the inflammatory response underlying wound healing. These processes consist of immune cell polarization, regulation of cytokines and chemokines, and signaling network dynamics, hence emphasis is laid on the canonical mechanism for maintaining steady-state tissue restoration, namely, immune homeostasis. Moreover, this review examines the dynamic cross-talk of growth factors, ECM components, and angiogenesis in different healing phases. An overview of novel interventions is also included such as negative pressure wound therapy (NPWT), hyperbaric oxygen, exosome-based approaches, biomaterial-based approaches, nanohydrogel systems, and microneedle-facilitated delivery, with insights into mechanisms and translational progress. Critical clinical translation barriers, including wound heterogeneity, host-microbe cross-talk, and limitations of model extrapolation as well as the potential application of multi-omics integration and an interdisciplinary approach towards precision wound healing, are discussed. Overall, regulation of inflammation is the foundation for the whole wound healing cascade, and immune homeostasis is a key prerequisite for injury repair. Tailored therapeutic strategies might thus greatly enhance healing outcomes and clinical efficacy.