Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, 380009, Gujarat, India.
AV Pharma LLC, 1545 University Blvd N Ste A, Jacksonville, Florida, 32211, USA.
Med Oncol. 2023 Oct 19;40(11):334. doi: 10.1007/s12032-023-02201-8.
Colorectal cancer (CRC) is a complex disease characterized by genetic and epigenetic alterations, playing a crucial role in its development and progression. This review aims to provide insights into the emerging landscape of these alterations in CRC pathogenesis to develop effective diagnostic tools and targeted therapies. Genetic alterations in signaling pathways such as Wnt/β-catenin, and PI3K/Akt/mTOR are pivotal in CRC development. Genetic profiling has identified distinct molecular subtypes, enabling personalized treatment strategies. Epigenetic modifications, including DNA methylation and histone modifications, also contribute to CRC pathogenesis by influencing critical cellular processes through gene silencing or activation. Non-coding RNAs have emerged as essential players in epigenetic regulation and CRC progression. Recent research highlights the interplay between genetic and epigenetic alterations in CRC. Genetic mutations can affect epigenetic modifications, leading to dysregulated gene expression and signaling cascades. Conversely, epigenetic changes can modulate genetic expression, amplifying or dampening the effects of genetic alterations. Advancements in understanding pathogenic pathways have potential clinical applications. Identifying genetic and epigenetic markers as diagnostic and prognostic biomarkers promises more accurate risk assessment and early detection. Challenges remain, including validating biomarkers and developing robust therapeutic strategies through extensive research and clinical trials. The dynamic nature of genetic and epigenetic alterations necessitates a comprehensive understanding of their temporal and spatial patterns during CRC progression. In conclusion, the genetic and epigenetic landscape of CRC is increasingly being unraveled, providing valuable insights into its pathogenesis. Integrating genetic and epigenetic knowledge holds great potential for improving diagnostics, prognostics, and personalized therapies in CRC. Continued research efforts are vital to translate these findings into clinical practice, ultimately improving patient outcomes.
结直肠癌(CRC)是一种复杂的疾病,其特征是遗传和表观遗传改变,在其发生和发展中起着关键作用。本综述旨在提供对这些改变在 CRC 发病机制中的新兴研究进展的深入了解,以开发有效的诊断工具和靶向治疗方法。信号通路如 Wnt/β-catenin 和 PI3K/Akt/mTOR 的遗传改变在 CRC 的发展中起着关键作用。遗传分析已经确定了不同的分子亚型,从而能够制定个性化的治疗策略。表观遗传修饰,包括 DNA 甲基化和组蛋白修饰,也通过基因沉默或激活影响关键的细胞过程,从而促进 CRC 的发病机制。非编码 RNA 已成为表观遗传调控和 CRC 进展的重要参与者。最近的研究强调了 CRC 中遗传和表观遗传改变之间的相互作用。遗传突变可以影响表观遗传修饰,导致基因表达和信号级联的失调。相反,表观遗传变化可以调节基因表达,放大或抑制遗传改变的影响。对发病机制途径的深入了解具有潜在的临床应用价值。确定遗传和表观遗传标记作为诊断和预后生物标志物有望进行更准确的风险评估和早期检测。挑战仍然存在,包括通过广泛的研究和临床试验验证生物标志物和开发强大的治疗策略。遗传和表观遗传改变的动态性质需要全面了解它们在 CRC 进展过程中的时间和空间模式。总之,CRC 的遗传和表观遗传景观正在被逐步揭示,为其发病机制提供了有价值的见解。整合遗传和表观遗传知识有望改善 CRC 的诊断、预后和个性化治疗。持续的研究努力对于将这些发现转化为临床实践至关重要,最终将改善患者的治疗效果。