Cancer is complex because of the critical imbalance in genetic regulation as characterized by both the overexpression of oncogenes (OGs), mainly through mutations, amplifications, and translocations, and the inactivation of tumor-suppressor genes (TSGs), which entail the preservation of genomic integrity by inducing apoptosis to counter the malignant growth. Reviewing the intricate molecular interplay between OGs and TSGs draws attention to their cell cycle, apoptosis, and cancer metabolism regulation. In the present review, we discuss seminal discoveries, such as Knudson’s two-hit hypothesis, which framed the field’s understanding of cancer genetics, leading to the next breakthroughs with next-generation sequencing and epigenetic profiling, revealing novel insights into OG and TSG dysregulation with opportunities for targeted therapy. The key pathways, such as MAPK/ERK, PI3K/AKT/mTOR, and Wnt/β-catenin, are presented in the context of tumor progression. Importantly, we further highlighted the advances in therapeutic strategies, including inhibitors of KRAS and MYC and restoration of TSG function, despite which mechanisms of resistance and tumor heterogeneity pose daunting challenges. A high-level understanding of interactions between OG-TSGs forms the basis for effective, personalized cancer treatment—something to strive for in better clinical outcomes. This synthesis should integrate foundational biology with translation and, in this case, contribute to the ongoing effort against cancer.
癌症的复杂性源于基因调控的关键失衡，主要表现为癌基因（OGs）的过度表达（主要通过突变、扩增和易位实现）以及肿瘤抑制基因（TSGs）的失活。TSGs通过诱导细胞凋亡来抑制恶性生长，从而维持基因组完整性。回顾OGs与TSGs之间复杂的分子相互作用，有助于聚焦它们在细胞周期、凋亡及癌症代谢调控中的关键作用。本综述探讨了该领域的里程碑式发现，如Knudson的二次打击假说，该假说奠定了癌症遗传学的理论基础，并推动了新一代测序和表观遗传分析等突破性技术的出现，这些技术揭示了OGs与TSGs失调的新机制，为靶向治疗提供了可能。文章在肿瘤进展的背景下阐述了MAPK/ERK、PI3K/AKT/mTOR和Wnt/β-catenin等关键信号通路。值得注意的是，我们进一步强调了治疗策略的进展，包括KRAS和MYC抑制剂的应用以及TSG功能恢复策略，尽管耐药机制和肿瘤异质性仍是严峻挑战。深入理解OGs与TSGs之间的相互作用，是开发有效个体化癌症治疗的基础，也是改善临床疗效的努力方向。本综述旨在整合基础生物学与转化医学研究，为持续的抗癌事业贡献力量。
肿瘤(癌症)患者之家