Department of Cancer Biology, Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Hum Vaccin Immunother. 2012 Aug;8(8):1141-2. doi: 10.4161/hv.19643. Epub 2012 Aug 1.
Despite significant improvements in diagnosis, surgical techniques, and advancements in general patient care, the majority of deaths from cancer are caused by the continuous growth of metastases that are resistant to conventional therapies. In a large number of cancer patients, metastasis may well have occurred by the time of diagnosis. The metastases can be located in different distant organs and in different regions within a single organ. The major obstacle for the eradication of metastases is the biologic heterogeneity of tumor cells that constitute primary cancers and metastases. Specifically, by the time of diagnosis, malignant neoplasms contain multiple cell populations with diverse biological heterogeneity in growth rate, karyotype, cell surface receptors, antigenicity, immunogenicity, maker enzymes, gene expression, sensitivity to different cytotoxic drugs, invasion, and metastasis. This biologic heterogeneity is not restricted to primary lesions. The cellular composition of metastases in the same organ or in different organs is heterogeneous, both within a single metastasis (intralesional heterogeneity) and among different metastases (interlesional heterogeneity). This heterogeneity is due to two major processes: the selective nature of the metastatic process, and the rapid evolution and phenotypic diversification of clonal tumor cell populations during progressive tumor growth resulting from inherent genetic and epigenetic instability of many clonal populations of tumor cells.
尽管在诊断、手术技术和一般患者护理方面取得了重大进展，但大多数癌症死亡仍是由于对传统疗法具有耐药性的转移持续生长所致。在大量癌症患者中，转移很可能在诊断时已经发生。转移可以位于不同的远处器官，也可以位于同一器官的不同区域。消除转移的主要障碍是构成原发性癌症和转移的肿瘤细胞的生物学异质性。具体而言，在诊断时，恶性肿瘤包含多个细胞群体，其在生长速度、核型、细胞表面受体、抗原性、免疫原性、标记酶、基因表达、对不同细胞毒性药物的敏感性、侵袭和转移方面具有不同的生物学异质性。这种异质性不仅限于原发性病变。同一器官或不同器官中的转移的细胞组成是异质的，无论是在单个转移灶内（灶内异质性）还是在不同转移灶之间（灶间异质性）都是如此。这种异质性归因于两个主要过程：转移过程的选择性以及由于许多肿瘤细胞克隆群体固有的遗传和表观遗传不稳定性，在进行性肿瘤生长过程中克隆肿瘤细胞群体的快速进化和表型多样化。
