Background

The transition of a primary tumour to metastatic progression is driven by dynamic molecular changes, including genetic and epigenetic alterations. The metastatic cascade involves bidirectional interactions among extracellular and intracellular components leading to disintegration of cellular junctions, cytoskeleton reorganization and epithelial to mesenchymal transition. These events promote metastasis by reprogramming the primary cancer cell’s molecular framework, enabling them to cause local invasion, anchorage-independent survival, cell death and immune resistance, extravasation and colonization of distant organs. Metastasis follows a site-specific pattern that is still poorly understood at the molecular level. Although various drugs have been tested clinically across different metastatic cancer types, it has remained difficult to develop efficacious therapeutics due to complex molecular layers involved in metastasis as well as experimental limitations.

Conclusions

In this review, a systemic evaluation of the molecular mechanisms of metastasis is outlined and the potential molecular components and their status as therapeutic targets and the associated pre-clinical and clinical agents available or under investigations are discussed. Integrative methods like pan-cancer data analysis, which can provide clinical insights into both targets and treatment decisions and help in the identification of crucial components driving metastasis such as mutational profiles, gene signatures, associated pathways, site specificities and disease-gene phenotypes, are discussed. A multi-level data integration of the metastasis signatures across multiple primary and metastatic cancer types may facilitate the development of precision medicine and open up new opportunities for future therapies.

中文翻译：

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破译转移的分子机制：对靶点和治疗的新见解

背景

原发性肿瘤向转移性进展的转变是由动态分子变化驱动的，包括遗传和表观遗传改变。转移级联涉及细胞外和细胞内成分之间的双向相互作用，导致细胞连接解体、细胞骨架重组和上皮细胞向间充质细胞转变。这些事件通过重新编程原发癌细胞的分子框架来促进转移，使它们能够引起局部侵袭、不依赖锚定的存活、细胞死亡和免疫抵抗、外渗和远处器官的定植。转移遵循在分子水平上仍然知之甚少的位点特异性模式。尽管已经在不同的转移性癌症类型中对各种药物进行了临床测试，

结论

在这篇综述中，概述了对转移的分子机制的系统评估，并讨论了潜在的分子成分及其作为治疗靶点的状态以及相关的临床前和临床药物可用或正在研究中。像泛癌数据分析这样的综合方法可以为靶点和治疗决策提供临床见解，并有助于识别驱动转移的关键成分，如突变谱、基因特征、相关途径、位点特异性和疾病基因表型。讨论过。跨多种原发性和转移性癌症类型的转移特征的多级数据集成可能会促进精准医学的发展，并为未来的治疗开辟新的机会。