Evaluating Clinical Applications of Liquid Biopsy by Combining Circulating Tumor DNA and Tumor cells
Abstract
"Liquid biopsy" concentrates on the identification of ‘Circulating Tumor Cells (CTC) as well as ‘Cell-free Tumor DNA’ (ctDNA) in the systemic circulation of individuals suffering from cancer, has received a lot of interest due to its evident clinical implications for individualized therapy. CTC and ctDNA studies have created fresh diagnostic approaches and are now the foundations of liquid biopsy. The existing study concentrates on cancer diagnoses, prognosis prediction in people having treatable diseases, observing systemic therapy, and patient categorization depending on the identification of aimed therapeutics or resistance mechanisms. Although the use of CTCs and ctDNA for initial cancer diagnosis is gaining popularity, existing techniques experience major challenges in terms of particularity and sensitivity. Prognosis projection in people with the treatable disease so far realized in some cancer entities, especially in breast cancer. Sequential assessments of CTCs or ctDNA can also be used to monitor the progress or non-success of systemic medicines (such as hormone and chemotherapy as well as various targeted therapies).To integrate liquid diagnostic tests into personalized medicine, interventional studies on therapy stratification based on CTC and ctDNA analyses are required.
References
2. Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA . J Clin Oncol 2014; 32 : 579 – 86.
3. Haber DA, Velculescu VE . Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA . Cancer Discov 2014; 4: 650 – 61.
4. Pantel K, Alix-Panabieres C. Real-time liquid biopsy in cancer patients: fact or fiction? Cancer Res 2013; 73: 6384 – 8.
5. Joseph JD , Lu N , Qian J , Sensintaffar J , Shao G , Brigham D , et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov 2013; 3: 1020 – 9.
6. Meng S , Tripathy D , Frenkel EP , Shete S , Naftalis EZ , Huth JF , et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004; 10: 8152 – 62.
7. Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients . Cancer Cell 2013; 23: 573 – 81.
8. Larson CJ , Moreno JG , Pienta KJ , Gross S , Repollet M , O’Hara S M , et al. Apoptosis of circulating tumor cells in prostate cancer patients . Cytometry A 2004; 62: 46 – 53.
9. Douillard JY, Ostoros G, Cobo M, Ciuleanu T , McCormack R , Webster A , et al. First-line gefi tinib in Caucasian EGFR mutationpositive NSCLC patients: a phase-IV, open-label, single-arm study . Br J Cancer 2014; 110: 55 – 62.
10. Deneve E , Riethdorf S , Ramos J , Nocca D , Coffy A , Daures JP , et al. Capture of viable circulating tumor cells in the liver of colorectal cancer patients . Clin Chem 2013; 59: 1384 – 92.
11. Smith HA , Kang Y. The metastasis-promoting roles of tumor associated immune cells. J Mol Med (Berl) 2013; 91: 411 – 29.
12. Gay LJ, Felding-Habermann B . Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011; 11: 123 – 34.
13. Bonecchi R , Galliera E , Borroni EM, Corsi MM, Locati M , Mantovani A. Chemokines and chemokine receptors: an overview . Front Biosci (Landmark Ed) 2009; 14: 540– 51.
14. Melo SA, Luecke LB , Kahlert C , Fernandez AF , Gammon ST, Kaye J, et al. Glypican-1 identifi es cancer exosomes and detects early pancreatic cancer . Nature 2015; 523: 177 – 82.
15. Muller V , Stahmann N , Riethdorf S , Rau T , Zabel T , Goetz A , et al. 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 – 85.
16. Kim MY , Oskarsson T , Acharyya S , Nguyen DX , Zhang XH , Norton L , et al. Tumor self-seeding by circulating cancer cells. Cell 2009; 139 : 1315 – 26.
17. Bidard FC , Peeters DJ , Fehm T , Nole F , Gisbert-Criado R , Mavroudis D, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data . Lancet Oncol 2014; 15: 406 – 14.
18. Braun S, Vogl FD , Naume B , Janni W , Osborne MP , Coombes RC , et al. A pooled analysis of bone marrow micrometastasis in breast cancer . N Engl J Med 2005; 353: 793 – 802.
19. Alix-Panabieres C , Pantel K . Challenges in circulating tumour cell research . Nat Rev Cancer 2014; 14: 623 – 31.
20. Mani SA , Guo W , Liao MJ , Eaton EN , Ayyanan A , Zhou AY , et al. The epithelial–mesenchymal transition generates cells with properties of stem cells . Cell 2008; 133: 704 – 15.
21. Tam WL , Weinberg RA . The epigenetics of epithelial–mesenchymal plasticity in cancer . Nat Med 2013; 19: 1438 – 49.
22. Antonarakis ES , Lu C , Wang H , Luber B , Nakazawa M , Roeser J C, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer . N Engl J Med 2014; 371: 1028 – 38.
23. Cayrefourcq L , Mazard T , Joosse S , Solassol J , Ramos J , Assenat E , et al. Establishment and characterization of a cell line from human circulating colon cancer cells . Cancer Res 2015; 75: 892 – 901.
24. Baccelli I, Schneeweiss A, Riethdorf S , Stenzinger A , Schillert A , Vogel V, et al. Identifi cation of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol. 2013; 31: 539 – 44.
25. Steinestel J, Luedeke M, Arndt A, Schnoeller TJ, Lennerz JK, W urm C , et al. Detecting predictive androgen receptor modifi cations in circulating prostate cancer cell. Oncotarget 2015 Apr 23. Epub ahead of print.
26. Kahlert C , Melo SA , Protopopov A , Tang J , Seth S , Koch M , et al. Identifi cation of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem 2014; 289: 3869 – 75.
27. Thakur BK , Zhang H , Becker A , Matei I , Huang Y , Costa-Silva B , et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection . Cell Res 2014; 24: 766 – 9.
28. Heitzer E , Auer M , Hoffmann EM , Pichler M , Gasch C , Ulz P , et al. Establishment of tumor-specifi c copy number alterations from plasma DNA of patients with cancer . Int J Cancer 2013; 133: 346 – 56 .
29. Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet 1999; 64: 218 – 24.
30. Elshimali YI , Khaddour H , Sarkissyan M , Wu Y , Vadgama JV . The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients . Int J Mol Sci 2013; 14: 18925 – 58.
31. Kirsch C , Weickmann S , Schmidt B , Fleischhacker M . An improved method for the isolation of free-circulating plasma DNA and cell-free DNA from other body fl uids . Ann N Y Acad Sci 2008; 1137: 135 – 9.
32. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426– 37.
33. Trejo-Becerril C , Perez-Cardenas E , Taja-Chayeb L, Anker P , Herrera- Goepfert R , Medina-Velazquez LA , et al. Cancer progression mediated by horizontal gene transfer in an in vivo model . PLoS One 2012; 7: e52754.
34. Satelli A, Brownlee Z, Mitra A, Meng QH, Li S. Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response . Clin Chem 2015; 61: 259 – 66.
35. De Lamirande G. Action of deoxyribonuclease and ribonuclease on the growth of Ehrlich ascites carcinoma in mice. Nature 1961; 192: 52 – 4 .
36. Pantel K , Alix-Panabieres C . Functional Studies on Viable Circulating Tumor Cells . Clin Chem 2016; 62: 328 – 34 .
37. Alix-Panabieres C, Pantel K . Liquid biopsy in cancer patients: advances in capturing viable CTCs for functional studies usingthe EPISPOT assay . Expert review of molecular diagnostics 2015; 15: 1411 – 7.
38. Heidary M , Auer M , Ulz P , Heitzer E , Petru E , Gasch C , et al. The dynamic range of circulating tumor DNA in metastatic breast cancer . Breast Cancer Res 2014; 16: 421.
39. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2015.
40. Murtaza M , Dawson SJ , Tsui DW , Gale D , Forshew T , Piskorz AM , et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108– 12.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.