Ling Zhang

Melanoma is characterized by profound intra‐tumoural heterogeneity and a complex tumour microenvironment (TME), which are primary drivers of therapy resistance. Conventional bulk sequencing lacks the resolution to capture these cellular nuances. Single‐cell technologies, particularly single‐cell RNA sequencing (scRNA‐seq) and spatial multiomics, have fundamentally advanced our understanding of melanoma by enabling high‐resolution characterization of malignant cell states, immune ecosystems and tumour microenvironment interactions. In this review, we summarize recent advances in single‐cell multiomics studies of melanoma heterogeneity and therapy resistance, focusing on the identification of drug‐tolerant persister states, immune escape mechanisms and resistance‐associated cellular transitions. We further discuss how single‐cell approaches facilitate target discovery, biomarker development and the rational design of combination therapies. By integrating multiomics profiling, computational modelling and pharmacological validation, these technologies provide a framework for translating cellular‐level insights into precision therapeutic strategies. Finally, we highlight current challenges and future opportunities for clinical implementation of single‐cell‐guided approaches in refractory melanoma.

Cancer currently stands as a formidable challenge confronting humanity. Patients afflicted with malignancies typically endure diminished survival rates and compromised quality of life. Consequently, the paramount objective of oncological research lies in redefining cancer from a terminal diagnosis to a clinically manageable condition, thereby realizing this transformative medical paradigm. The development of multiple innovative therapeutic strategies may enhance the antitumor immune response. Notably, pyroptosis is considered both a form of programmed cell death and a highly inflammatory type of immunogenic cell death. Its activation may accelerate cancer cell death and exert antitumor effects as a promising scenario to reverse immunosuppression. This article elaborates on the following three main aspects: the molecular mechanisms underlying pyroptosis and the development of promising therapeutics that target pyroptosis, the relationship between pyroptosis, inflammation, and tumors, and the application of nano-targeting materials in tumor treatments. These interactive therapeutic patterns may catalyze a paradigm shift in oncology. In this review, we probe the synergistic effects of pyroptosis and nanomaterials, forecast achievements in the field of tumor treatments, detail optimized therapeutic strategies, and shed promising light on the potential for the improvement and development of clinical drugs based on pyroptosis.