The MYC oncogene family constitutes a master regulatory hub in tumorigenesis, with functional complexity extending far beyond individual gene activities. Recent advances unveil cooperative yet context‐dependent antagonism and dynamic interplay among MYC family members, fundamentally reshaping our understanding of lineage specific oncogenic programs. This review synthesizes emerging insights into MYC orchestrated tumor microenvironment remodeling, reciprocal regulation with noncoding RNAs, and the transcriptional and epigenetic governance of metabolic reprogramming. We delineate mechanisms by which MYC drives therapeutic resistance and critically evaluate current strategies targeting MYC or its downstream networks, encompassing direct MYC–MAX disruptors, upstream pathway inhibitors, synthetic lethality, and combinatorial regimens with immune checkpoint blockade or conventional chemotherapy. We further discuss MYC's prognostic significance across diverse cancer types, the critical gap between preclinical efficacy and clinical outcomes, and emerging combination strategies aimed at overcoming acquired drug resistance. By integrating these rapidly evolving biological dimensions, we posit MYC as a highly multidimensional regulatory node whose context‐dependent functions present both formidable challenges and promising new opportunities for effective therapeutic intervention.
Na Zhang, Li Wei, Cuiping Tang et al.· MedComm· 0 citations
Sirtuins (SIRT1–SIRT7) are nicotinamide adenine dinucleotide (NAD+) dependent deacylases that serves as metabolic sensors, coupling cellular energy status to chromatin structure, mitochondrial function, and stress responses. Dysregulated SIRT activity has been extensively studied in aging, metabolic syndrome, cardiovascular disease, neurodegeneration, cancer, and immune disorders. However, robust human evidence and SIRT‐targeted therapies are lacking. Transgenic mouse models serve as key platforms to study gene function and guide therapeutic development. This review synthesizes evidence from Sirt1–7 transgenic mouse models regarding the core cellular processes governed by SIRTs: metabolism, genome integrity, stress resistance, immunity, and autophagy, and illustrates their operation across different organ systems. By comparing global, tissue‐specific, and inducible knockout (KO) and overexpression (OE) models of cardiovascular, respiratory, digestive, nervous, endocrine, urogenital, musculoskeletal, malignant, and immune diseases, we identified central regulatory SIRTs (SIRT1, SIRT3, and SIRT6), context‐dependent modifiers (SIRT2, SIRT4, SIRT5, and SIRT7), and their organ‐ and cell type‐specific functions. We also summarize representative small‐molecule SIRT activators, inhibitors, and degraders, covering both clinical and preclinical studies, and highlight where contradictions and knowledge gaps remain. Together, these analyses help clarify which aspects of SIRT modulation are most promising and under what isoform, tissue, and disease contexts they should be pursued for the development of SIRT‑targeted therapies in human disease.