Miyamoto David T, Ting David T, Toner Mehmet, Maheswaran Shyamala, Haber Daniel A
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114.
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Cold Spring Harb Symp Quant Biol. 2016;81:269-274. doi: 10.1101/sqb.2016.81.031120. Epub 2017 Apr 7.
Recent advances in microfluidic approaches have enabled the efficient isolation and detailed molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of patients with cancer. Single-cell molecular analyses of CTCs reveal a tremendous degree of intracellular heterogeneity in CTC populations, reflective of heterogeneity across different patients as well as the underlying heterogeneity of tumors within each individual patient. These studies have enabled the identification of heterogeneous drug resistance mechanisms that can coexist in treatment refractory tumors. CTC analyses also enable serial noninvasive monitoring in patients and can capture the emergence of tumor heterogeneity over time, whether due to tumor evolution through genetic instability or through cellular plasticity. The presence and extent of intratumoral heterogeneity as revealed through the study of CTCs have important clinical implications for understanding and predicting the development of treatment resistance in a variety of solid tumors and for formulating appropriate therapeutic strategies in the effective treatment of cancer.
微流控技术的最新进展使得从癌症患者外周血中高效分离循环肿瘤细胞（CTC）并对其进行详细的分子特征分析成为可能。对CTC的单细胞分子分析揭示了CTC群体中存在高度的细胞内异质性，这反映了不同患者之间的异质性以及每个患者体内肿瘤的潜在异质性。这些研究有助于识别在治疗难治性肿瘤中可能共存的异质性耐药机制。CTC分析还能够对患者进行连续的无创监测，并能够捕捉肿瘤异质性随时间的出现情况，这可能是由于肿瘤通过基因不稳定或细胞可塑性发生进化所致。通过对CTC的研究揭示的肿瘤内异质性的存在和程度，对于理解和预测各种实体瘤治疗耐药性的发展以及制定有效的癌症治疗适当策略具有重要的临床意义。
