2012年1月16日，據(jù)《每日科學(xué)》報(bào)道,，德國(guó)腫瘤基因組研究中心（GENYO）的研究人員已經(jīng)鑒定出能導(dǎo)致腫瘤發(fā)展和轉(zhuǎn)移的基因變化及表型變化。腫瘤轉(zhuǎn)移的過(guò)程--這是癌癥致死的主要原因,，是由腫瘤細(xì)胞入侵與最初受染器官無(wú)解剖學(xué)關(guān)系的遠(yuǎn)處器官所致,。為了做到這一點(diǎn)，這些腫瘤細(xì)胞（稱(chēng)之為"循環(huán)腫瘤細(xì)胞",，CTCs）有必要通過(guò)血液循環(huán)到達(dá)這些遠(yuǎn)處的器官,。
研究人員在一位接受全身性治療的乳腺癌患者體內(nèi)檢測(cè)到了正在進(jìn)行細(xì)胞分裂的循環(huán)腫瘤細(xì)胞（CTCs）。從而證明循環(huán)腫瘤細(xì)胞（CTCs）能夠適應(yīng)諸如血液這樣的惡劣環(huán)境,，抵抗藥物治療并在其他組織和器官中分裂和增殖,，最終導(dǎo)致轉(zhuǎn)移。到目前為止,，還沒(méi)有在這類(lèi)微環(huán)境中觀察到這種行為,。
研究的結(jié)果發(fā)表在Cancer Biology & Therapy、Clinical Translational Oncoloy及Annals of Oncology上,，文章題目為"Biodynamics of Circulating Tumor Cell, Tumor Microenvironment and Metastasis（循環(huán)腫瘤細(xì)胞,、腫瘤微環(huán)境及轉(zhuǎn)移的生物動(dòng)力學(xué)）",。研究人員發(fā)現(xiàn)循環(huán)腫瘤細(xì)胞（CTCs）處于基線(xiàn)水平的乳腺癌患者傾向于發(fā)生轉(zhuǎn)移并在治療后有較短的無(wú)病生存期（Disease-Free Survival，DFSs）,。因此,，在治療期間及治療后檢測(cè)循環(huán)腫瘤細(xì)胞（CTCs）使醫(yī)生能夠識(shí)別哪些患者對(duì)化療有積極的回應(yīng)。結(jié)果,，含有循環(huán)腫瘤細(xì)胞（CTCs）的患者盡管接受了化療,，只有一個(gè)較短的無(wú)病生存期和較低的總生存率（Overall Survival Rate，OSR）,。這是由于這些循環(huán)腫瘤細(xì)胞（CTCs）對(duì)依據(jù)腫瘤的遺傳學(xué)特征而開(kāi)展的常規(guī)治療有抵抗作用,。因此，CTCs能夠逃過(guò)化療并轉(zhuǎn)移到其他器官,。
更有效的個(gè)性化治療
格拉納達(dá)大學(xué)教授,、GENYO經(jīng)理主任及研究組的協(xié)調(diào)員José Antonio Lorente博士確信，循環(huán)腫瘤細(xì)胞（CTCs）的研究至關(guān)重要,，不僅因?yàn)樗鼈冐?fù)責(zé)轉(zhuǎn)移的發(fā)生,，還因?yàn)樗鼈兣c原發(fā)腫瘤細(xì)胞和轉(zhuǎn)移細(xì)胞有不同的遺傳學(xué)特征。這種特征使這些極具侵略性的細(xì)胞能夠抵抗機(jī)體的免疫系統(tǒng)及常規(guī)的化療藥物,。"這些治療大多針對(duì)的是腫瘤細(xì)胞的增殖,。相反，循環(huán)腫瘤細(xì)胞（CTCs）被發(fā)現(xiàn)處于一種"冬眠"階段,，例如"非增殖"階段,。
由于這些細(xì)胞可能指示對(duì)治療的陰性反應(yīng)，如果將它們分離出來(lái)并進(jìn)行遺傳學(xué)鑒定,，就可以根據(jù)復(fù)發(fā)的機(jī)會(huì)對(duì)患者進(jìn)行分類(lèi),，進(jìn)行后續(xù)的個(gè)性化治療。
"Biodynamics of Circulating Tumor Cell, Tumor Microenvironment and Metastasis"研究組由María José Serrano Fernández, José Luis García Puche, Pedro Sánchez Rovira, Juan Carlos Alvarez, Lucas González Herrera, Laura Vera Rodríguez, José Javier López Caballero and José Antonio Lorente組成,。該研究小組已經(jīng)對(duì)這項(xiàng)研究結(jié)果進(jìn)行了相關(guān)的專(zhuān)利注冊(cè),。該國(guó)際性項(xiàng)目依賴(lài)于羅氏制藥、盤(pán)古（Pangaea）及Tromso大學(xué)（挪威）Inigo Martínez Zubiau教授的參與,。（生物谷bioon.com）
PMID: 21421466
PMC:
PMID:
Circulating tumour cells in peripheral blood: potential impact on breast cancer outcome.
Serrano MJ, Lorente JA, Delgado Rodríguez M, Fernández A, Fernández M, de la Torre C, Fernández Izquierdo J, Sánchez Rovira P.
Abstract: INTRODUCTION: In breast cancer, the metastatic process may involve the dissemination of circulating tumour cells (CTCs) through the blood and lymphatic system prior to the colonisation of distant organs. Here we demonstrate the predictive capacity of CTCs for detecting risk of death in breast cancer patients during established time intervals. METHODS: CTCs were identified by immunocytochemical methods following isolation by selective immunomagnetic cell separation of cytokeratin-positive cells. Serial blood samples from 65 patients were collected at roughly monthly intervals for up to 50 months. Follow-up was conducted at different intervals: 1-5, >5-12, >12-24 and >24-50 months. RESULTS: Both presence and number of CTCs were correlated to risk of death: patients with CTCs at any time during follow-up had a higher risk of death (p=0.035) than patients without CTCs. Furthermore, during the first 5 months of therapy, patients with >5 CTCs had a higher risk of death than patients with <5 CTCs (p=0.002). CONCLUSIONS: Our results show that the persistence of CTCs after chemotherapy, particularly during the first 5 months, could define a group of patients with a high risk of relaps.
Genomic Oncology | Genyo
Group name: Biodynamics of circulating tumor cells, tumor microenvironment and metastasis
SCIENTIFIC INTEREST AREAS： Biological implications of CTCs in the metastatic process: Control of growth and tumor dormancy The systemic nature of breast cancer is defined by the dissemination of early tumor cells, even with relatively small tumors. In this scenario, the metastatic process may involve the dissemination of circulating tumor cells (CTCs) through the blood and lymphatic system prior to the colonization of distant organs. Several studies have regarded CTCs in peripheral blood as the pre-stadium of clinically manifest distant metastases. Furthermore, recent evidence have validated the prognostic capacity of CTCs, and highlighted the importance of CTCs analyses in those patients without clinical evidence of metastasis. As a result of acquired chemoresistance, an increasing number of patients experience disease progression following first-line chemotherapy. In this context, the prognostic role of CTCs might prove critical in efforts to predict risk of further metastases and in the therapeutic decision process.
