S-adenosylmethionine (SAMe) is a key methyl donor that plays a critical role in a variety of cellular processes, such as DNA, RNA and protein methylation, essential for maintaining genomic stability, regulating gene expression and maintaining cellular homeostasis. The involvement of SAMe in cancer pathogenesis is multifaceted, as through its multiple cellular functions, it can influence tumor initiation, progression and therapeutic resistance. In addition, the connection of SAMe with polyamine synthesis and oxidative stress management further underscores its importance in cancer biology. Recent studies have highlighted the potential of SAMe as a biomarker for cancer diagnosis and prognosis. Furthermore, the therapeutic implications of SAMe are promising, with evidence suggesting that SAMe supplementation or modulation could improve the efficacy of existing cancer treatments by restoring proper methylation patterns and mitigating oxidative damage and protect against damage induced by chemotherapeutic drugs. Moreover, targeting methionine cycle enzymes to both regulate SAMe availability and SAMe-independent regulatory effects, particularly in methionine-dependent cancers such as colorectal and lung cancer, presents a promising therapeutic approach. Additionally, exploring epitranscriptomic regulations, such as m6A modifications, and their interaction with non-coding RNAs could enhance our understanding of tumor progression and resistance mechanisms. Precision medicine approaches integrating patient subtyping and combination therapies with chemotherapeutics, such as decitabine or doxorubicin, together with SAMe, can enhance chemosensitivity and modulate epigenomics, showing promising results that may improve treatment outcomes. This review comprehensively examines the various roles of SAMe in cancer pathogenesis, its potential as a diagnostic and prognostic marker, and its emerging therapeutic applications. While SAMe modulation holds significant promise, challenges such as bioavailability, patient stratification and context-dependent effects must be addressed before clinical implementation. In addition, better validation of the obtained results into specific cancer animal models would also help to bridge the gap between research and clinical practice.
S-腺苷甲硫氨酸（SAMe）是一种关键的甲基供体，在多种细胞过程中发挥重要作用，如DNA、RNA和蛋白质的甲基化，这些过程对维持基因组稳定性、调控基因表达和保持细胞稳态至关重要。SAMe在癌症发病机制中的作用是多方面的，通过其多种细胞功能，它可以影响肿瘤的发生、进展和治疗抵抗。此外，SAMe与多胺合成和氧化应激管理的联系进一步凸显了其在癌症生物学中的重要性。最近的研究强调了SAMe作为癌症诊断和预后生物标志物的潜力。此外，SAMe的治疗应用前景广阔，有证据表明，补充或调节SAMe可以通过恢复正常的甲基化模式、减轻氧化损伤以及保护免受化疗药物诱导的损伤，从而提高现有癌症治疗的效果。此外，靶向甲硫氨酸循环酶以调节SAMe的可用性和SAMe非依赖性调控效应，特别是在结直肠癌和肺癌等甲硫氨酸依赖性癌症中，是一种有前景的治疗方法。另外，探索表观转录组调控（如m6A修饰）及其与非编码RNA的相互作用，可以增强我们对肿瘤进展和耐药机制的理解。整合患者亚型分型和联合疗法（如地西他滨或多柔比星与SAMe联合使用）的精准医学方法可以提高化疗敏感性并调控表观基因组，显示出可能改善治疗结果的良好前景。本综述全面探讨了SAMe在癌症发病机制中的各种作用、其作为诊断和预后标志物的潜力以及其新兴的治疗应用。尽管SAMe调控具有重要前景，但在临床实施之前，必须解决生物利用度、患者分层和背景依赖性效应等挑战。此外，在特定的癌症动物模型中更好地验证所得结果也将有助于弥合研究与临床实践之间的差距。
S-Adenosylmethionine: A Multifaceted Regulator in Cancer Pathogenesis and Therapy
肿瘤(癌症)患者之家