• D.V. SCRIPCARIU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • C.D. LUPASCU “Grigore T. Popa” University of Medicine and Pharmacy Iasi


Rectal cancer treatment has been continuously improving in the past decades and research has rightly been directed for this purpose, because this is a major public health issue. On the other hand, circulating tumor cells have emerged in the past two decades as an important element in oncology, because of the large potential they offer. They have been studied mostly in breast cancer and have already been implemented as a tool in certain strategies in this field. Thus, circulating tumor cells in rectal cancer may have the same important applicability, with a wide range of usages, from screening to diagnostics, guidance of the treatment and even follow-up. This article aims to review the literature and exhibit data about the pathophysiology, utility and methods of identification of circulating tumor cells with focus on their link to rectal cancer.

Author Biographies

D.V. SCRIPCARIU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Medicine
Department of Surgery (I)
Regional Institute of Oncology Iasi
First Surgical Unit

C.D. LUPASCU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Medicine
Department of Surgery (I)
“Sf. Spiridon” County Clinical Emergency Hospital Iasi
Second Surgical Unit


1. Urtishak S, Alpaugh RK, Weiner LM, Swaby RF. Clinical utility of circulating tumor cells: a role for monitoring response to therapy and drug development. Biomarkers in Medicine 2008; 2(2): 137-145.
2. ***GLOBOCAN 2012 v 1.0, cancer incidence and mortality worldwide: IARC cancer base no. 11 (Internet). International Agency for Research on Cancer, Lyon.
3. Burt RW, Cannon JA, David DS, Early DS, Ford JM, Giardiello FM et al. Colorectal cancer screening. Journal of the National Comprehensive Cancer Network 2013; 11(12): 1538-1575.
4. Warren JL, Klabunde CN, Mariotto AB, Meekins A, Topor M, Brown ML, et al. Adverse events after outpatient colonoscopy in the Medicare population. Annals of Internal Medicine 2009; 150(12): 849-857.
5. Shapiro JA, Bobo JK, Church TR, Rex DK, Chovnick G, Thompson TD, et al. A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening. The American Journal of Gastroenterology. 2017.
6. Hol L, van Leerdam ME, van Ballegooijen M, van Vuuren AJ, van Dekken H, Reijerink JC, et al. Screening for colorectal cancer: randomized trial comparing guaiac-based and immunochemical fecal occult blood testing and flexible sigmoidoscopy. Gut 2010; 59(1): 62-68.
7. Ahlquist DA, Sargent DJ, Loprinzi CL, Levin TR, Rex DK, Ahnen DJ, et al. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Annals of Internal Medicine. 2008; 149(7): 441-450.
8. Swedish Rectal Cancer T, Cedermark B, Dahlberg M, Glimelius B, Pahlman L, Rutqvist LE, et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. The New England Journal of Medicine 1997; 336(14): 980-987.
9. Bujko K, Nasierowska-Guttmejer A, Wyrwicz L, Malinowska M, Krynski J, Kosakowska E, et al. Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicenter randomized study. Radiotherapy and Oncology 107(2): 171-177.
10. Ashworth T. A case of cancer in which cells similar to those in the tumors were see in the blood after death. Aust. Med. J. 1869; 14: 146-149.

11. Ram H. Datar ZA, and Richard J. Cote. Significance of Studying Circulating Tumor Cells. In: Richard J. Cote RHD, editor. Circulating Tumor Cells - Advances in Basic Science and Clinical Applications. New York: Springer, 2016.
12. Noam Falbel Pondé MI. Circulating Tumor Cells in Primary Disease: The Seed for Metastasis. In: Cristofanilli M, editor. Liquid Biopsies in Solid Tumors. Chicago: Springer, 2017.
13. Butler TP, Gullino PM. Quantitation of cell shedding into efferent blood of mammary adenocarcinoma. Cancer research 1975; 35(3): 512-516.
14. Ignatiadis M, Lee M, Jeffrey SS. Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility. Clinical Cancer Research. 2015; 21(21): 4786-4800.
15. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016; 35(10): 1216-1224.
16. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011; 147(2): 275-292.
17. van Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: cell invasion and endothelial transmi-gration. Mutation research 2011; 728(1-2): 23-34.
18. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation 2009; 119(6): 1420-1428.
19. Coumans FA, Siesling S, Terstappen LW. Detection of cancer before distant metastasis. BMC Cancer 2013; 13: 283.
20. Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, et al. Circulating tumor cells in patients with breast cancer dormancy. Clinical Cancer Research: 2004; 10(24): 8152-8162.
21. Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, et al. The identification and characteri-zation of breast cancer CTCs competent for brain metastasis. Science Translational Medicine. 2013; 5(180): 180ra48.
22. Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H. Seeding and propagation of untransformed mouse mammary cells in the lung. Science 2008; 321(5897): 1841-1844.
23. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012; 148(1-2): 349-361.
24. Pantel K, Alix-Panabieres C. Circulating tumor cells in cancer patients: challenges and perspectives. Trends in Molecular Medicine 2010; 16(9): 398-406.
25. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. Journal of Clinical Oncology 2014; 32(31): 3483-3489.
26. ***AJCC Cancer Staging Manual. Amin MB et al (editors) New York: Springer International Pub-lishing, 2017.
27. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. The New England Journal of Medicine. 2004; 351(8): 781-791.
28. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Annals of Oncology 2009; 20(7): 1223-1239.
29. Shih-Min A. Huang MRL. CTCs for Biomarker and Companion Diagnostic Development. In: Richard J. Cote RHD, editor. Circulating Tumor Cells - Advances in Basic Science and Clinical Applications. New York: Springer; 2016.
30. Zheng Ao RJC, Ram H. Datar. Affinity-Based Enrichment of Circulating Tumor Cells. In: Datar RJCRH, editor. Circulating Tumor Cells-Advances in Basic Science and Clinical Applications. New York: Springer, 2016.
31. Zheng Ao KM, Richard J. Cote, Ram H. Datar. Size-Based and Non-Affinity Based Microfluidic Devices for Circulating Tumor Cell Enrichment and Characterization. In: Zheng Ao KM, Richard J. Cote, and Ram H. Datar, editor. Circulating Tumor Cells - Advances in Basic Science and Clinical Applications. New York: Springer; 2016.
32. Gleghorn JP, Pratt ED, Denning D, Liu H, Bander NH, Tagawa ST et al. Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential im-munocapture (GEDI) and a prostate-specific antibody. Lab on a Chip 2010; 10(1): 27-29.