Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.

Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven.

[1]  Sin-Ho Jung,et al.  Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02) , 2016, Oncotarget.

[2]  T. Wurdinger,et al.  Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer , 2015, Oncotarget.

[3]  C. Schumann,et al.  Enumeration and Molecular Characterization of Tumor Cells in Lung Cancer Patients Using a Novel In Vivo Device for Capturing Circulating Tumor Cells , 2015, Clinical Cancer Research.

[4]  Shuang Hou,et al.  A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer , 2015, Oncotarget.

[5]  T. Fest,et al.  Frequent expression of PD‐L1 on circulating breast cancer cells , 2015, Molecular oncology.

[6]  B. Kermani,et al.  Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA , 2015, PloS one.

[7]  Geoffrey R. Oxnard,et al.  Bias-Corrected Targeted Next-Generation Sequencing for Rapid, Multiplexed Detection of Actionable Alterations in Cell-Free DNA from Advanced Lung Cancer Patients , 2015, Clinical Cancer Research.

[8]  P. Jänne,et al.  Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses , 2015, Clinical Cancer Research.

[9]  Chia-Jung Yu,et al.  Circulating Messenger RNA Profiling with Microarray and Next-generation Sequencing: Cross-platform Comparison. , 2015, Cancer genomics & proteomics.

[10]  S. Stein,et al.  Circulating Cell-Free Tumour DNA in the Management of Cancer , 2015, International journal of molecular sciences.

[11]  P. Jänne,et al.  AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. , 2015, The New England journal of medicine.

[12]  J. Neal,et al.  Rociletinib in EGFR-mutated non-small-cell lung cancer. , 2015, The New England journal of medicine.

[13]  T. Mok,et al.  Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy , 2015, Clinical Cancer Research.

[14]  V. Wong,et al.  Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients , 2015, Proceedings of the National Academy of Sciences.

[15]  M. Erlander,et al.  Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders. , 2015, Cancer discovery.

[16]  Chung-Liang Ho,et al.  Noninvasive saliva-based EGFR gene mutation detection in patients with lung cancer. , 2014, American journal of respiratory and critical care medicine.

[17]  Marius Ilie,et al.  Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? , 2014, Annals of translational medicine.

[18]  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.

[19]  N. Girard,et al.  Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002 , 2014, Clinical Cancer Research.

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

[21]  Gary J. W. Liao,et al.  Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing , 2014, Proceedings of the National Academy of Sciences.

[22]  T. Yap,et al.  Circulating Tumor Cells: A Multifunctional Biomarker , 2014, Clinical Cancer Research.

[23]  A. Jemal,et al.  Annual Report to the Nation on the status of cancer, 1975‐2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer , 2014, Cancer.

[24]  Caroline Dive,et al.  Molecular analysis of circulating tumour cells—biology and biomarkers , 2014, Nature Reviews Clinical Oncology.

[25]  M. Choti,et al.  Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies , 2014, Science Translational Medicine.

[26]  C. Paweletz,et al.  Noninvasive Detection of Response and Resistance in EGFR-Mutant Lung Cancer Using Quantitative Next-Generation Genotyping of Cell-Free Plasma DNA , 2014, Clinical Cancer Research.

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

[28]  Marta Di Nicola,et al.  microRNAs Derived from Circulating Exosomes as Noninvasive Biomarkers for Screening and Diagnosing Lung Cancer , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[29]  Jae Cheol Lee,et al.  Detection of EGFR mutations in circulating free DNA by PNA-mediated PCR clamping , 2013, Journal of experimental & clinical cancer research : CR.

[30]  C. Marquette,et al.  ALK-gene rearrangement: a comparative analysis on circulating tumour cells and tumour tissue from patients with lung adenocarcinoma. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[31]  Massimo Cristofanilli,et al.  Considerations in the development of circulating tumor cell technology for clinical use , 2012, Journal of Translational Medicine.

[32]  E. Cisneros,et al.  Analysis of exosome release and its prognostic value in human colorectal cancer , 2012, Genes, chromosomes & cancer.

[33]  Caroline Dive,et al.  Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Koichi Goto,et al.  Epidermal Growth Factor Receptor Mutation Status in Circulating Free DNA in Serum: From IPASS, a Phase III Study of Gefitinib or Carboplatin/Paclitaxel in Non-small Cell Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[35]  M. Ychou,et al.  High Fragmentation Characterizes Tumour-Derived Circulating DNA , 2011, PloS one.

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

[37]  Caroline Dive,et al.  Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  S. Digumarthy,et al.  Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors , 2011, Science Translational Medicine.

[39]  E. Kroh,et al.  Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma , 2011, Proceedings of the National Academy of Sciences.

[40]  Yama W. L. Zheng,et al.  Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus , 2010, Science Translational Medicine.

[41]  T. Molina,et al.  Preoperative Circulating Tumor Cell Detection Using the Isolation by Size of Epithelial Tumor Cell Method for Patients with Lung Cancer Is a New Prognostic Biomarker , 2010, Clinical Cancer Research.

[42]  Larry Norton,et al.  Tumor Self-Seeding by Circulating Cancer Cells , 2009, Cell.

[43]  L. Mao,et al.  Epidermal growth factor receptor mutations in plasma DNA samples predict tumor response in Chinese patients with stages IIIB to IV non-small-cell lung cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  Michael Morse,et al.  Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  K. Nishio,et al.  Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA) , 2007, British Journal of Cancer.

[46]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[47]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.

[48]  D. Chan,et al.  Increased plasma DNA integrity in cancer patients. , 2003, Cancer research.