Considerations in the development of circulating tumor cell technology for clinical use

Journal of Translational Medicine

Gary J Kelloff^1,19  Caroline C Sigman⁵  Howard I Scher^1,18  Andrew E Schade^1,12  Lori T Roadcap⁶  Elizabeth A Punnoose^1,16  Sonia Pearson-White^1,13  Klaus Pantel²  Larry Nagahara^1,19  Stanislaw Mikulski⁸  Robert McCormack¹  Minetta C Liu⁴  Jerry SH Lee^1,19  Prasanna Kumar^1,10  Gordon Kapke^1,17  Daniel F Hayes^1,15  Albert Deisseroth³  Massimo Cristofanilli⁷  Carolyn Compton^1,14  Brenda Gumbs Petty⁵  Nicholas Dracopoli^1,11  David R Parkinson⁹ 

[1] Veridex, LLC, Raritan, NJ, 08869, USA;University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany;Center for Drug Evaluation Research, US Food & Drug Administration, Silver Spring, MA, 20903, USA;Georgetown University, Washington, DC, 20007, USA;CCS Associates, Mountain View, CA, 94043, USA;GlaxoSmithKline, Collegeville, PA, 19426, USA;Fox Chase Cancer Center, Philadelphia, PA, 19111, USA;EMD Serono, Rockland, MA, 02370, USA;New Enterprise Associates, Menlo Park, CA 94025, USA;Daiichi-Sankyo Pharma Development, Edison, NJ, 08837, USA;Johnson &Johnson, Radnor, PA, 19087, USA;Eli Lilly and Company, Indianapolis, IN, 46285, USA;Foundation for the National Institutes of Health, Bethesda, MA, 20814, USA;Critical Path Institute, Tucson, AZ, 85718, USA;University of Michigan, Ann Arbor, MI, 48109, USA;Genentech, South San Francisco, CA, 94080, USA;Covance Genomic Lab, Covance Central Labs, Seattle, WA, 98382, USA;Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA;National Cancer Institute, Bethesda, MA, 20892, USA

关键词: Oncologic drug development;    Biomarker qualification;    Clinical validation;    Analytical validation;    Predictive biomarker;    Prognostic biomarker;    Circulating tumor cells;   

Others  :  1205943
DOI  :  10.1186/1479-5876-10-138

 received in 2012-04-21, accepted in 2012-06-14,  发布年份 2012

【 摘 要 】

This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).

【 授权许可】

   
2012 Parkinson et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Yu M, Stott S, Toner M, Maheswaran S, Haber DA: Circulating tumor cells: approaches to isolation and characterization. J Cell Biol 2011, 192:373-382.
• [2]Nelson NJ: Circulating tumor cells: will they be clinically useful? J Natl Cancer Inst 2010, 102:146-148.
• [3]Hou JM, Krebs M, Ward T, Morris K, Sloane R, Blackhall F, Dive C: Circulating tumor cells, enumeration and beyond. Cancers 2010, 2:1236-1250.
• [4]Nagrath S, Stott SL, Lee RJ, Yu M, Ulkus LL, Iafrate JA, Smith MR, Tompkins RG, Sequist LV, Haber DA, Maheswaran S, Toner M: Detection and characterization of circulating tumor cells in localized and metastatic prostate cancer patients using CTC-Chip microfluidic technology. Proc Am Assoc Cancer Res 2010, 101st:abstr 1136.
• [5]Bertolin M, Pigozzo J, Koussis H, Ghiotto C, Valente S, Michieletto S, Magro C, Rossi E, Zamarchi R, Bozza F, Jirillo A, Chiarion-Sileni V, Amadori A: Circulating tumor cells detection and evaluation of their apoptotic status in patients with localized breast cancer before and after surgery. J Clin Oncol 2011, 29(suppl):abstr e21127.
• [6]Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A, Janicke F, Pantel K: Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 2005, 11:3678-3685.
• [7]Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 2007, 450:1235-1239.
• [8]Pierga JY, Bidard FC, Mathiot C, Brain E, Delaloge S, Giachetti S, de Cremoux P, Salmon R, Vincent-Salomon A, Marty M: Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 2008, 14:7004-7010.
• [9]Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M, Roller M, Huober J, Fehm T, Schrader I, Hilfrich J, Holms F, Tesch H, Eidtmann H, Untch M, von Minckwitz G, Pantel K: Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res 2010, 16:2634-2645.
• [10]Xenidis N, Ignatiadis M, Apostolaki S, Perraki M, Kalbakis K, Agelaki S, Stathopoulos EN, Chlouverakis G, Lianidou E, Kakolyris S, Georgoulias V, Mavroudis D: Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol 2009, 27:2177-2184.
• [11]Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, Leach SD, Stanger BZ: EMT and dissemination precede pancreatic tumor formation. Cell 2012, 148:349-361.
• [12]Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S: Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 2009, 11:R46. BioMed Central Full Text
• [13]Polyak K, Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009, 9:265-273.
• [14]Bednarz N, Eltze E, Semjonow A, Rink M, Andreas A, Mulder L, Hannemann J, Fisch M, Pantel K, Weier HU, Bielawski KP, Brandt B: BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. Clin Cancer Res 2010, 16:3340-3348.
• [15]Joosse SA, Hannemann J, Spotter J, Bauche A, Andreas A, Muller V, Pantel K: Changes in keratin expression during metastatic progression of breast cancer: impact on the detection of circulating tumor cells. Clin Cancer Res 2012, 18:993-1003.
• [16]Lilly B, Kennard S: Differential gene expression in a coculture model of angiogenesis reveals modulation of select pathways and a role for Notch signaling. Physiol Genomics 2009, 36:69-78.
• [17]Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK, Floyd FP, Gilman AJ, Lord JB, Winokur D, Springer S, Irimia D, Nagrath S, Sequist LV, Lee RJ, Isselbacher KJ, Maheswaran S, Haber DA: Toner M: Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A 2010, 107:18392-18397.
• [18]Hou JM, Krebs M, Ward T, Sloane R, Priest L, Hughes A, Clack G, Ranson M, Blackhall F, Dive C: Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 2011, 178:989-996.
• [19]Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Priest LJ, Greystoke A, Zhou C, Morris K, Ward T, Blackhall FH, Dive C: Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 2012, 30:525-532.
• [20]Molnar B, Ladanyi A, Tanko L, Sreter L, Tulassay Z: Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Cancer Res 2001, 7:4080-4085.
• [21]Serrano Fernadez MJ, Alvarez Merino JC, Martinez Zubiaurre I, Fernandez Garcia A, Sanchez Rovira P, Lorente Acosta JA: Clinical relevance associated to the analysis of circulating tumor cells in patients with solid tumors. Clin Transl Oncol 2009, 11:668-659.
• [22]Wang ZP, Eisenberger MA, Carducci MA, Partin AW, Scher HI, Ts’o PO: Identification and characterization of circulating prostate carcinoma cells. Cancer 2000, 88:2787-2795.
• [23]Glinsky VV, Glinsky GV, Glinskii OV, Huxley VH, Turk JR, Mossine VV, Deutscher SL, Pienta KJ, Quinn TP: Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Cancer Res 2003, 63:3805-3811.
• [24]Pantel K, Deneve E, Nocca D, Coffy A, Vendrell JP, Maudelonde T, Riethdorf S, Alix-Panabieres C: Circulating epithelial cells in patients with benign colon diseases. Clin Chem 2012, 58:936-940.
• [25]Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janicke F, Jackson S, Gornet T, Cristofanilli M, Pantel K: Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res 2007, 13:920-928.
• [26]Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch P, Khan A, Euhus D, Osborne C, Frenkel E, Hoover S, Leitch M, Clifford E, Vitetta E, Morrison L, Herlyn D, Terstappen LW, Fleming T, Fehm T, Tucker T, Lane N, Wang J, Uhr J: HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A 2004, 101:9393-9398.
• [27]Wulfing P, Borchard J, Buerger H, Heidl S, Zanker KS, Kiesel L, Brandt B: HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 2006, 12:1715-1720.
• [28]Chang HJ, Han SW, Oh DY, Im SA, Jeon YK, Park IA, Han W, Noh DY, Bang YJ, Kim TY: Discordant human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancer and response to trastuzumab. Jpn J Clin Oncol 2011, 41:593-599.
• [29]Alix-Panabieres C, Schwarzenbach H, Pantel K: Circulating tumor cells and circulating tumor DNA. Annu Rev Med 2012, 63:199-215.
• [30]Wang LH, Pfister TD, Parchment RE, Kummar S, Rubinstein L, Evrard YA, Gutierrez ME, Murgo AJ, Tomaszewski JE, Doroshow JH, Kinders RJ: Monitoring drug-induced gammaH2AX as a pharmacodynamic biomarker in individual circulating tumor cells. Clin Cancer Res 2010, 16:1073-1084.
• [31]Maheswaran S, Haber DA: Circulating tumor cells: a window into cancer biology and metastasis. Curr Opin Genet Dev 2010, 20:96-99.
• [32]Lianidou ES, Markou A: Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem 2011, 57:1242-1255.
• [33]Ignatiadis M, Rothe F, Chaboteaux C, Durbecq V, Rouas G, Criscitiello C, Metallo J, Kheddoumi N, Singhal SK, Michiels S, Veys I, Rossari J, Larsimont D, Carly B, Pestrin M, Bessi S, Buxant F, Liebens F, Piccart M, Sotiriou C: HER2-positive circulating tumor cells in breast cancer. PLoS One 2011, 6:e15624.
• [34]US Food and Drug Administration: Guidance for Industry: Qualification Process for Drug Development Tools. Draft Guidance. 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM230597.pdf webcite
• [35]US Food and Drug Administration: Guidance for Industry: Pharmacogenomic Data Submissions. 2005.
• [36]US Food and Drug Administration: Draft Guidance for Industry and Food and Drug Administration Staff: In Vitro Companion Diagnostic Devices Draft Guidance. 2011. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf webcite
• [37]McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 2005, 97:1180-1184.
• [38]Shaffer DR, Leversha MA, Danila DC, Lin O, Gonzalez-Espinoza R, Gu B, Anand A, Smith K, Maslak P, Doyle GV, Terstappen LW, Lilja H, Heller G, Fleisher M, Scher HI: Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res 2007, 13:2023-2029.
• [39]Serrano MJ, Sanchez-Rovira P, Delgado-Rodriguez M, Gaforio JJ: Detection of circulating tumor cells in the context of treatment: prognostic value in breast cancer. Cancer Biol Ther 2009, 8:671-675.
• [40]Danila DC, Anand A, Sung CC, Heller G, Leversha MA, Cao L, Lilja H, Molina A, Sawyers CL, Fleisher M, Scher HI: TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Eur Urol 2011, 60:897-904.
• [41]Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Lohberg CR, Solomayer E, Rack B, Riethdorf S, Klein C, Schindlbeck C, Brocker K, Kasimir-Bauer S, Wallwiener D, Pantel K: HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 2010, 124:403-412.
• [42]Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004, 351:781-791.
• [43]de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D: Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008, 14:6302-6309.
• [44]Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, Meropol NJ: Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 2008, 26:3213-3221.
• [45]Rink M, Chun FK, Dahlem R, Soave A, Minner S, Hansen J, Stoupiec M, Coith C, Kluth LA, Ahyai SA, Friedrich MG, Shariat SF, Fisch M, Pantel K, Riethdorf S: Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Eur Urol 2012, 61:810-817.
• [46]Naoe M, Ogawa Y, Morita J, Omori K, Takeshita K, Shichijyo T, Okumura T, Igarashi A, Yanaihara A, Iwamoto S, Fukagai T, Miyazaki A, Yoshida H: Detection of circulating urothelial cancer cells in the blood using the Cell Search System. Cancer 2007, 109:1439-1445.
• [47]Okumura Y, Tanaka F, Yoneda K, Hashimoto M, Takuwa T, Kondo N, Hasegawa S: Circulating tumor cells in pulmonary venous blood of primary lung cancer patients. Ann Thorac Surg 2009, 87:1669-1675.
• [48]Steen S, Nemunaitis J, Fisher T, Kuhn J: Circulating tumor cells in melanoma: a review of the literature and description of a novel technique. Proc (Bayl Univ Med Cent) 2008, 21:127-132.
• [49]Gradilone A, Naso G, Raimondi C, Cortesi E, Gandini O, Vincenzi B, Saltarelli R, Chiapparino E, Spremberg F, Cristofanilli M, Frati L, Aglianò AM, Gazzaniga P: Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization. Ann Oncol 2011, 22:86-92.
• [50]Pantel K, Brakenhoff RH, Brandt B: Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008, 8:329-340.
• [51]Meng S, Tripathy D, Shete S, Ashfaq R, Saboorian H, Haley B, Frenkel E, Euhus D, Leitch M, Osborne C, Clifford E, Perkins S, Beitsch P, Khan A, Morrison L, Herlyn D, Terstappen LW, Lane N, Wang J, Uhr J: uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci U S A 2006, 103:17361-17365.
• [52]Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA: Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008, 359:366-377.
• [53]Bidard FC, Mathiot C, Degeorges A, Etienne-Grimaldi MC, Delva R, Pivot X, Veyret C, Bergougnoux L, de Cremoux P, Milano G, Pierga JY: Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy. Ann Oncol 2010, 21:1765-1771.
• [54]Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, Matera J, Repollet M, Doyle GV, Terstappen LW, Hayes DF: Circulating tumor cells versus imaging–predicting overall survival in metastatic breast cancer. Clin Cancer Res 2006, 12:6403-6409.
• [55]Allan AL, Keeney M: Circulating tumor cell analysis: technical and statistical onsiderations for application to the clinic. J Oncol 2010, 2010:426218.
• [56]Adams AA, Okagbare PI, Feng J, Hupert ML, Patterson D, Göttert J, McCarley RL, Nikitopoulos D, Murphy MC, Soper SA: Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. J Am Chem Soc 2008, 130:8633-8641.
• [57]Kirby BJ, Jodari M, Loftus MS, Gakhar G, Pratt ED, Chanel-Vos C, Gleghorn JP, Santana SM, Liu H, Smith JP, Navarro NV, Tagawa ST, Bander NH, Nanus DM, Giannakakou P: Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One 2012, 7:e35976. Epub 32012 Apr 35927
• [58]Dancey JE, Dobbin KK, Groshen S, Jessup JM, Hruszkewycz AH, Koehler M, Parchment R, Ratain MJ, Shankar LK, Stadler WM, True LD, Gravell A: Grever MR; Biomarkers Task Force of the NCI Investigational Drug Steering Committee: Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res 2010, 16:1745-1755.
• [59]Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW: Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004, 10:6897-6904.
• [60]Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW: Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004, 10:8152-8162.
• [61]Smerage JB, Doyle GV, Budd GT, Schott AF, Blayney DW, Wicha MS, Repollet M, Terstappen LW, Hayes DF: The detection of apoptosis and Bcl-2 expression in circulating tumor cells (CTCs) from women being treated for metastatic breast cancer. Proc Am Assoc Cancer Res 2006, 47:abstr 792.
• [62]Taube SE, Clark GM, Dancey JE, McShane LM, Sigman CC, Gutman SI: A perspective on challenges and issues in biomarker development and drug and biomarker codevelopment. J Natl Cancer Inst 2009, 101:1453-1463.
• [63]Lianidou ES: Circulating tumor cells--new challenges ahead. Clin Chem 2012, 58:805-807.
• [64]Hayes DF, Smerage J: Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 2008, 14:3646-3650.
• [65]Reyal F, Valet F, de Cremoux P, Mathiot C, Decraene C, Asselain B, Brain E, Delaloge S, Giacchetti S, Marty M, Pierga JY, Bidard FC: Circulating tumor cell detection and transcriptomic profiles in early breast cancer patients. Ann Oncol 2011, 22:1458-1459.