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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2017, Vol. 11 Issue (4) : 522-527    https://doi.org/10.1007/s11684-017-0526-7
REVIEW
Application of liquid biopsy in precision medicine: opportunities and challenges
Junyun Wang, Shuang Chang, Guochao Li, Yingli Sun()
Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
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Abstract

Precision medicine for cancer patients aims to adopt the most suitable treatment options during diagnosis and treatment of individuals. Detecting circulating tumor cell (CTC) or circulating tumor DNA (ctDNA) in plasma or serum could serve as liquid biopsy, which would be useful for numerous diagnostic applications. Liquid biopsies can help clinicians screen and detect cancer early, stratify patients to the most suitable treatment and real-time monitoring of treatment response and resistance mechanisms in the tumor, evaluate the risk for metastatic relapse, and estimate prognosis. We summarized the advantages and disadvantages of tissue and liquid biopsies. We also further compared and analyzed the advantages and limitations of detecting CTCs, ctDNAs, and exosomes. Furthermore, we reviewed the literature related with the application of serum or plasma CTCs, ctDNAs, and exosomes for diagnosis and prognosis of cancer. We also analyzed their opportunities and challenges as future biomarkers. In the future, liquid biopsies could be used to guide cancer treatment. They could also provide the ideal scheme to personalize treatment in precision medicine.
Keywords liquid biopsy      circulating tumor cells      cell-free ctDNA      exosomes      precision medicine     
Corresponding Author(s): Yingli Sun   
Just Accepted Date: 02 June 2017   Online First Date: 25 July 2017    Issue Date: 04 December 2017
 Cite this article:   
Junyun Wang,Shuang Chang,Guochao Li, et al. Application of liquid biopsy in precision medicine: opportunities and challenges[J]. Front. Med., 2017, 11(4): 522-527.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0526-7
https://academic.hep.com.cn/fmd/EN/Y2017/V11/I4/522
SubjectAdvantageDisadvantage
Tissue biopsyStandard detection procedure
Specific mutations that are helpful to target therapies		Suffered and invasive
Not real-time detection
Some tumors, such as that in lung, are not accessible for biopsy
Information provided by biopsy is static, and it becomes inaccurate with cancer progression
Needs multiple biopsies and is expensive
Unavailable tumor sample
Intratumor heterogeneity
Inability to obtain tumor samples at different stages of disease
Liquid
biopsy		Non-invasive
Real-time detection
Collects samples repeatedly and multiple detection during treatment
Provides considerably comprehensive information
Responds to surgery and therapy effects
More sensitive as biomarkers than that of tissue biopsy		Significantly low amounts of circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) and considerable amount of blood sample needed
ctDNA and CTC levels remarkably vary among individuals, and they are difficult to detect.
Needs validation in large studies
Confined to the clinical application of advanced cancer
Tab.1  Advantages and disadvantages of tissue and liquid biopsies [2,5,6]
Fig.1  Origin of CTCs and ctDNAs in blood plasma. CtDNAs and exosomes were secreted from necrotic and apoptotic tumor cells, and CTCs were released from tumor tissue. Gene mutation and epigenetic DNA methylation can be detected as diagnostic and prognostic biomarkers of cancer.
Fig.2  Clinical applications of liquid biopsy for precision medicine. CTCs, ctDNAs, and exosomes as liquid biopsy for precision medicine, including screening and early detection of cancer, real-time monitoring of therapy, stratification and therapeutic intervention, therapeutic target and resistance mechanism, risk for metastatic relapse (prognosis), and improvement of drug delivery with exosomes.
SubjectAdvantagesLimitations
CTCsPhenotypic studies of intact cells from tumor, including cell morphology and protein localization
Relevance for metastatic process and disease progression
Allow functional in vitro/in vivo assays
Opportunity for molecular characterization at both cellular and subcellular levels
Allow immunolabeling-based approaches
Complementary with ctDNA: CTCs can escape from current chemotherapy
Potentially influence changes in treatment modalities		Heterogeneity of the CTC populations (e.g., detection of CTCs with tumor-initiating capacity)
Low abundance and fragility
Require considerably sensitive and specific analytic methods
False-negative (due to tumor metastasis) and false-positive results
Multiplicity of technologies used for CTC isolation
ctDNAsSensitivity for detection of disease burden
Complementary with CTCs for detection of minimal residual disease after surgery or therapy with curative intent
Might predict acquired drug resistance
Potentially influence changes in treatment modalities		False-negative/false-positive results (e.g., no specific isolation of ctDNA or mutations of tumor-associated genes in frequent benign diseases)
No functional assays
Lack of standardization of preanalytical conditions
ExosomesAnalyzing RNA, DNA, and protein profiles from tumor cells
Analyzing inflammatory response, stromal, and other systemic changes
Used for drug delivery		Did not analyze the phenotypic studies of cells from tumor
Difficult extraction
Tab.2  Advantages and limitations of detecting CTCs, ctDNAs, and exosomes [20,38,41]
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