Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes—tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival—can help to understand the genomic causes behind tumorigenesis, leading to more personalized approaches to diagnosis and treatment. Aberration of tumor suppressors, which undergo two-hit and loss-of-function mutations, and oncogenes, activated forms of proto-oncogenes that experience one-hit and gain-of-function mutations, are responsible for the dysregulation of key signaling pathways that regulate cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, and Wnt/β-catenin. Modern breakthroughs in genomics research, like next-generation sequencing, have provided efficient strategies for mapping unique genomic changes that contribute to tumor heterogeneity. Novel therapeutic approaches have enabled personalized medicine, helping address genetic variability in tumor suppressors and oncogenes. This comprehensive review examines the molecular mechanisms behind tumor-suppressor genes and oncogenes, the key signaling pathways they regulate, epigenetic modifications, tumor heterogeneity, and the drug resistance mechanisms that drive carcinogenesis. Moreover, the review explores the clinical application of sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, and personalized treatment and prevention options, discussing future directions for emerging technologies.
癌症以细胞不受控制的增殖为特征，是全球主要死亡原因之一，约五分之一的人在一生中会罹患此病。尽管许多驱动基因在数十年前已被发现，且大多数癌症可根据形态学和进展程度进行分类，但关于遗传畸变和核DNA损伤的认识仍存在显著空白。研究两类关键基因——抑制增殖并促进凋亡的抑癌基因，以及调控增殖与存活的癌基因——有助于理解肿瘤发生背后的基因组学成因，从而推动更个性化的诊疗方法。抑癌基因通过二次打击和功能缺失突变发生畸变，而癌基因作为原癌基因的激活形式，则经历单次打击和功能获得性突变，两者共同导致调控细胞分裂的关键信号通路失调，例如p53、Rb、Ras/Raf/ERK/MAPK、PI3K/AKT和Wnt/β-catenin通路。基因组学研究的新突破，如新一代测序技术，为绘制导致肿瘤异质性的独特基因组变化提供了高效策略。新型治疗方法推动了个体化医疗的发展，有助于应对抑癌基因和癌基因的遗传变异。本综述系统探讨了抑癌基因与癌基因的分子作用机制、其调控的关键信号通路、表观遗传修饰、肿瘤异质性以及驱动癌变的耐药机制。此外，本文还深入分析了测序技术、多组学、诊断流程、药物基因组学及个体化治疗与预防策略的临床应用，并对新兴技术的未来发展方向进行了展望。
Translational Advances in Oncogene and Tumor-Suppressor Gene Research
肿瘤(癌症)患者之家