Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Nat Rev Drug Discov. 2012 Jun 1;11(6):479-97. doi: 10.1038/nrd2372.
Nearly all deaths caused by solid cancers occur as a result of metastasis--the formation of secondary tumours in distant organs such as the lungs, liver, brain and bone. A major obstruction to the development of drugs with anti-metastatic efficacy is our fragmented understanding of how tumours 'evolve' and metastasize, at both the biological and genetic levels. Furthermore, although there is significant overlap in the metastatic process among different types of cancer, there are also marked differences in the propensity to metastasize, the extent of metastasis, the sites to which the tumour metastasizes, the kinetics of the process and the mechanisms involved. Here, we consider the case of breast cancer, which has some marked distinguishing features compared with other types of cancer. Considerable progress has been made in the development of preclinical models and in the identification of relevant signalling pathways and genetic regulators of metastatic breast cancer, and we discuss how these might facilitate the development of novel targeted anti-metastatic drugs.
几乎所有由实体癌引起的死亡都是由于转移导致的——在肺部、肝脏、大脑和骨骼等远处器官形成继发性肿瘤。阻碍具有抗转移疗效的药物发展的一个主要障碍是我们对肿瘤在生物和遗传水平上“进化”和转移的理解是支离破碎的。此外，尽管不同类型的癌症在转移过程中有显著的重叠，但转移的倾向、转移的程度、肿瘤转移的部位、转移过程的动力学和涉及的机制也有明显的差异。在这里，我们以乳腺癌为例，它与其他类型的癌症相比具有一些明显的特征。在开发临床前模型以及鉴定转移性乳腺癌相关信号通路和遗传调节剂方面已经取得了相当大的进展，我们讨论了这些进展如何促进新型靶向抗转移药物的开发。
