2013.11.18 -- 李奇Selection and adaptation during metastatic cancer progression.pdfVIP

PERSPECTIVE doi:10.1038/nature12628 Selection and adaptation during metastatic cancer progression Christoph A. Klein1,2 Cancer is often regarded as a process of asexual evolution driven by genomic and genetic instability. Mutation, selection and adaptation are by convention thought to occur primarily within, and to a lesser degree outside, the primary tumour. However, disseminated cancer cells that remain after ‘curative’ surgery exhibit extreme genomic heterogeneity before the manifestation of metastasis. This heterogeneity is later reduced by selected clonal expansion, suggesting that the disseminated cells had yet to acquire key traits of fully malignant cells. Abrogation of the cells’ progression outside the primary tumour implies new challenges and opportunities for diagnosis and adjuvant therapies. oncern that progress in treating patients with epithelium- or Hallmarks of benign lesions and malignant cancer neuroectoderm-derived cancers is simply too slow is increas- It might be helpful to recall the basic characteristics of cancer before Cing. Notwithstanding the great enthusiasm about the potential considering systemic progression in detail. Malignant epithelial for improvements to cancer treatment that was evoked by cancer tumours are able to form vascularized colonies (metastases) at different genome projects and the cancer stem-cell concept in the past decade, sites in the body, whereas benign tumours cannot. By definition, then, targeted therapies currently prolong the lives of patients with metas- cancers can invade and metastasize. However, the molecular differences tasis by only a few weeks or months1–4. Moreover, they often have little between benign and mal