循环肿瘤细胞在临床应用中的研究进展

doi:10.3760/cma.j.issn.1673-422X.2018.09.009

摘要/Abstract

摘要： 循环肿瘤细胞（CTC）是从原发肿瘤或转移瘤脱落进入血液循环的肿瘤细胞。CTC目前被美国食品药品管理局（FDA）批准的临床适应证是可作为转移性乳腺癌、转移性前列腺癌和转移性结直肠癌患者的预后标志物。CTC在其他转移性或局限性肿瘤的预后评估，以及在肿瘤的早期筛查、分子表达谱的分析、治疗方案的制定及治疗效果的监测等方面也具有巨大的潜力。目前各项研究正在开展以深入挖掘CTC的临床应用潜力，为肿瘤患者的个体化精准治疗提供新策略和新前景。

关键词: 肿瘤循环细胞, 诊断, 预后, 液体活检

Abstract: Circulating tumor cells (CTCs) are cancerous cells that shed from the primary tumor or metastases into the bloodstream. The currently clinical applicability of CTCs approved by the US Food and Drug Administration (FDA) is that CTCs can be prognostic biomarker for patients with metastatic breast cancer, prostate cancer and colorectal cancer. CTCs also have great potential in the prognosis assessment of other metastatic or localized tumors, as well as early screening of tumors, analysis of molecular profiling, guiding treatment decisions, and monitoring of treatment response. Currently, various studies are being carried out to further explore the clinical application of CTCs, and provide new strategies and new prospects for individualized and precise treatment of cancer patients.

Key words: Neoplasm circulating cells, Diagnosis, Prognosis, Liquid biopsy

陈罗军，李娜，田景媛，宋启斌，于金明. 循环肿瘤细胞在临床应用中的研究进展[J]. 国际肿瘤学杂志, 2018, 45(8): 552-555.

Chen Luojun, Li Na, Tian Jingyuan, Song Qibin, Yu Jinming. Progress of circulating tumor cells in clinical application[J]. Journal of International Oncology, 2018, 45(8): 552-555.

参考文献

［1］ Cabel L, Proudhon C, Gortais H, et al. Circulating tumor cells: clinical validity and utility［J］. Int J Clin Oncol, 2017, 22(3): 421430. DOI: 10.1007/s1014701711052. ［2］ Bidard FC, Peeters DJ, Fehm T, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data［J］. Lancet Oncol, 2014, 15(4): 406414. DOI: 10.1016/S14702045(14)700695. ［3］ Huang X, Gao P, Song Y, et al. Metaanalysis of the prognostic value of circulating tumor cells detected with the CellSearch System in colorectal cancer［J］. BMC Cancer, 2015, 15: 202. DOI: 10.1186/s1288501512189. ［4］ Unger JM, Griffin K, Donaldson GW, et al. Patientreported outcomes for patients with metastatic castrationresistant prostate cancer receiving docetaxel and atrasentan versus docetaxel and placebo in a randomized phase Ⅲ clinical trial (SWOG S0421)［J］. J Patient Rep Outcomes, 2017, 2: 27. DOI: 10.1186/s4168701800545. ［5］ Krebs MG, Sloane R, Priest L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with nonsmallcell lung cancer［J］. J Clin Oncol, 2011, 29(12): 15561563. DOI: 10.1200/JCO.2010.28.7045. ［6］ Bidard FC, Michiels S, Riethdorf S, et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a metaanalysis［J］. J Natl Cancer Inst, 2018, 110(6): 560567. DOI: 10.1093/jnci/djy018. ［7］ Bork U, Rahbari NN, Scholch S, et al. Circulating tumour cells and outcome in nonmetastatic colorectal cancer: a prospective study［J］. Br J Cancer, 2015, 112(8): 13061313. DOI: 10.1038/bjc.2015.88. ［8］ Syrigos K, Fiste O, Charpidou A, et al. Circulating tumor cells count as a predictor of survival in lung cancer［J］. Crit Rev Oncol Hematol, 2018, 125: 6068. DOI: 10.1016/j.critrevonc.2018.03.004. ［9］ Davis JW, Nakanishi H, Kumar VS, et al. Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer［J］. J Urol, 2008, 179(6): 21872191. DOI: 10.1016/j.juro.2008.01.102. ［10］ Fiorelli A, Accardo M, Carelli E, et al. Circulating tumor cells in diagnosing lung cancer: clinical and morphologic analysis［J］. Ann Thorac Surg, 2015, 99(6): 18991905. DOI: 10.1016/j.athoracsur.2014.11.049. ［11］ Ilie M, Hofman V, LongMira E, et al. "Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease［J］. PLoS One, 2014, 9(10): e111597. DOI: 10.1371/journal.pone.0111597. ［12］ Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lungcancer cells［J］. N Engl J Med, 2008, 359(4): 366377. DOI: 10.1056/NEJMoa0800668. ［13］ Sundaresan TK, Sequist LV, Heymach JV, et al. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive bloodbased analyses［J］. Clin Cancer Res, 2016, 22(5): 11031110. DOI: 10.1158/10780432.Ccr151031. ［14］ Mostert B, Jiang Y, Sieuwerts AM, et al. KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue［J］. Int J Cancer, 2013, 133(1): 130141. DOI: 10.1002/ijc.27987. ［15］ Mohamed Suhaimi NA, Foong YM, Lee DY, et al. Noninvasive sensitive detection of KRAS and BRAF mutation in circulating tumor cells of colorectal cancer patients［J］. Mol Oncol, 2015, 9(4): 850860. DOI: 10.1016/j.molonc.2014.12.011. ［16］ Wang CH, Chang CJ, Yeh KY, et al. The prognostic value of HER2positive circulating tumor cells in breast cancer patients: a systematic review and metaanalysis［J］. Clin Breast Cancer, 2017, 17(5): 341349. DOI: 10.1016/j.clbc.2017.02.002. ［17］ Fehm T, Muller V, Aktas B, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial［J］. Breast Cancer Res Treat, 2010, 124(2): 403412. DOI: 10.1007/s105490101163x. ［18］ Miyamoto DT, Zheng Y, Wittner BS, et al. RNASeq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance［J］. Science, 2015, 349(6254): 13511356. DOI: 10.1126/science.aab0917. ［19］ Antonarakis ES, Lu C, Luber B, et al. Clinical significance of androgen receptor splice variant7 mRNA detection in circulating tumor cells of men with metastatic castrationresistant prostate cancer treated with first and secondline abiraterone and enzalutamide［J］. J Clin Oncol, 2017, 35(19): 21492156. DOI: 10.1200/JCO.2016.70.1961. ［20］ Georgoulias V, Bozionelou V, Agelaki S, et al. Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapyresistant CK19mRNApositive circulating tumor cells: results of a randomized phase Ⅱ study［J］. Ann Oncol, 2012, 23(7): 17441750. DOI: 10.1093/annonc/mds020. ［21］ Hainsworth JD, Murphy PB, Alemar JR, et al. Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2negative metastatic breast cancer: lack of response to HER2targeted therapy［J］. Breast Cancer Res Treat, 2016, 160(1): 4149. DOI: 10.1007/s1054901639697. ［22］ Krebs MG, Renehan AG, Backen A, et al. Circulating tumor cell enumeration in a phase Ⅱ trial of a fourdrug regimen in advanced colorectal cancer［J］. Clin Colorectal Cancer, 2015, 14(2): 115122. DOI: 10.1016/j.clcc.2014.12.006. ［23］ Goodman OB Jr, Symanowski JT, Loudyi A, et al. Circulating tumor cells as a predictive biomarker in patients with hormonesensitive prostate cancer［J］. Clin Genitourin Cancer, 2011, 9(1): 3138. DOI: 10.1016/j.clgc.2011.04.001. ［24］ Pearl ML, Dong H, Tulley S, et al. Treatment monitoring of patients with epithelial ovarian cancer using invasive circulating tumor cells (iCTCs)［J］. Gynecol Oncol, 2015, 137(2): 229238. DOI: 10.1016/j.ygyno.2015.03.002. ［25］ Smerage JB, Barlow WE, Hortobagyi GN, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500［J］. J Clin Oncol, 2014, 32(31): 34833489. DOI: 10.1200/jco.2014.56.2561.

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