Liquid Biopsy: Current Status and Future Perspectives

Cancer patients usually receive therapies according to their primary tumor's molecular traits. These characteristics may change during the molecular evolution of distant metastases as the leading cause of cancer deaths. Primary tumor tissue, if accessible at all, does not always provide enough information to stratify individual patients to the most promising therapy. Re-analysis of metastatic lesions by needle biopsy is possible but invasive, and limited by the known intra-patient heterogeneity of individual lesions. These hurdles might be overcome by analyzing tumor cells or tumor cell products in blood samples (liquid biopsy), which in principle might reflect all subclones present at that specific time point and allow sequential monitoring of disease evolution. Liquid biopsies inform on circulating tumor cells as well as tumor-derived cell-free nucleic acids, exosomes and platelets. Here, we introduce the different approaches of blood-based liquid biopsies and discuss the clinical applications in oncology.

[1]  Sridhar Ramaswamy,et al.  Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition , 2013, Science.

[2]  Richard J Simpson,et al.  A protocol for exosome isolation and characterization: evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. , 2015, Methods in molecular biology.

[3]  S. Minner,et al.  Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. , 2012, European urology.

[4]  Crispin J. Miller,et al.  Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer , 2016, Nature Medicine.

[5]  Ash A. Alizadeh,et al.  An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage , 2013, Nature Medicine.

[6]  K. Pantel,et al.  Tumour microenvironment: informing on minimal residual disease in solid tumours , 2017, Nature Reviews Clinical Oncology.

[7]  Klaus Pantel,et al.  Liquid Biopsies, What We Do Not Know (Yet). , 2017, Cancer cell.

[8]  M. Giacca,et al.  Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage. , 2015, Exercise immunology review.

[9]  R. McCormack,et al.  Gefitinib Treatment in EGFR Mutated Caucasian NSCLC , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[10]  Klaus Pantel,et al.  Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. , 2016, Cancer discovery.

[11]  C. Parker,et al.  Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study. , 2012, The Lancet. Oncology.

[12]  James D. Brenton,et al.  Liquid biopsies come of age: towards implementation of circulating tumour DNA , 2017, Nature Reviews Cancer.

[13]  Klaus Pantel,et al.  Circulating Tumor DNA as a Cancer Biomarker: Fact or Fiction? , 2016, Clinical chemistry.

[14]  Klaus Pantel,et al.  Clinical prospects of liquid biopsies , 2017, Nature Biomedical Engineering.

[15]  Raghu Kalluri,et al.  The biology and function of exosomes in cancer. , 2016, The Journal of clinical investigation.

[16]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

[17]  C. Croce Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[18]  Pieter Wesseling,et al.  RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics , 2015, Cancer cell.

[19]  Mahmood Ayub,et al.  Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer , 2014, Nature Medicine.

[20]  Udo Schumacher,et al.  Establishment and characterization of a cell line from human circulating colon cancer cells. , 2015, Cancer research.

[21]  Johan Skog,et al.  Liquid biopsy for cancer screening, patient stratification and monitoring , 2018 .

[22]  M R Speicher,et al.  The biology of circulating tumor cells , 2016, Oncogene.

[23]  T. Fehm,et al.  Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. , 2014, The Lancet. Oncology.

[24]  Gary K. Schwartz,et al.  Tumour exosome integrins determine organotropic metastasis , 2015, Nature.

[25]  Peter Ulz,et al.  Circulating tumor DNA as a liquid biopsy for cancer. , 2015, Clinical chemistry.

[26]  Ash A. Alizadeh,et al.  Integrated digital error suppression for improved detection of circulating tumor DNA , 2016, Nature Biotechnology.

[27]  W. Isaacs,et al.  AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. , 2014, The New England journal of medicine.

[28]  B. Shapiro,et al.  Free DNA in the serum of cancer patients and the effect of therapy. , 1977, Cancer research.

[29]  T. Wurdinger,et al.  Blood platelets contain tumor-derived RNA biomarkers. , 2011, Blood.

[30]  Tao Wang,et al.  Meta-Analysis of the Prognostic Value of Circulating Tumor Cells in Breast Cancer , 2012, Clinical Cancer Research.

[31]  M. Agostini,et al.  Telomere-Specific Reverse Transcriptase (hTERT) and Cell-free RNA in Plasma as Predictors of Pathologic Tumor Response in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy , 2012, Annals of Surgical Oncology.

[32]  A novel blood collection device stabilizes cell-free RNA in blood during sample shipping and storage , 2013, BMC Research Notes.

[33]  Sridhar Ramaswamy,et al.  Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility , 2014, Science.

[34]  Gema Moreno-Bueno,et al.  Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET , 2012, Nature Medicine.

[35]  G. Calin,et al.  Clinical relevance of circulating cell-free microRNAs in cancer , 2014, Nature Reviews Clinical Oncology.

[36]  Tim Holland-Letz,et al.  Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay , 2013, Nature Biotechnology.

[37]  Sarah Webb,et al.  The cancer bloodhounds , 2016, Nature Biotechnology.

[38]  K. Pantel,et al.  Challenges in circulating tumour cell research , 2014, Nature Reviews Cancer.

[39]  Tomasz Burzykowski,et al.  Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[41]  A. Vannucchi,et al.  Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer , 2016, Oncotarget.

[42]  K. Pantel,et al.  Epithelial-mesenchymal plasticity in circulating tumor cells , 2016, Journal of Molecular Medicine.

[43]  N. Rosenfeld,et al.  Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA , 2013, Nature.

[44]  Klaus Pantel,et al.  Tumor metastasis: moving new biological insights into the clinic , 2013, Nature Medicine.

[45]  M. Ferrari,et al.  New trend in non-invasive prenatal diagnosis. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[46]  Klaus Pantel,et al.  [The circulating tumor cells: liquid biopsy of cancer]. , 2014, Klinicheskaia laboratornaia diagnostika.

[47]  A. D'Ascola,et al.  Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease , 2015, Stem cells international.

[48]  K. Pantel,et al.  Technologies for detection of circulating tumor cells: facts and vision. , 2014, Lab on a chip.

[49]  K. Pantel,et al.  Real-time liquid biopsy in cancer patients: fact or fiction? , 2013, Cancer research.

[50]  Mark J. Ratain,et al.  Tumour heterogeneity in the clinic , 2013, Nature.

[51]  K. Pantel,et al.  Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. , 2015, Cancer cell.

[52]  M. Speicher,et al.  Tumor signatures in the blood , 2014, Nature Biotechnology.

[53]  Lilia Coronato Courrol,et al.  Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker. , 2014, The Analyst.

[54]  Peter Ulz,et al.  The dynamic range of circulating tumor DNA in metastatic breast cancer , 2014, Breast Cancer Research.

[55]  K. Pantel,et al.  Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of Patients with Squamous Cell Carcinoma of the Oral Cavity , 2013, Clinical Cancer Research.