Liquid Biopsy Revolutionizes the Precise Management of Tumors Across the Entire Course: Current Situation and Future Prospects

ZENG Jin, ZHANG Jun

Abstract

Tumors represent a global public-health concern, accounting for approximately one-sixth of all fatalities worldwide annually. Attaining precise management of patients across all stages of diagnosis, treatment, and surveillance is not merely a significant challenge in contemporary clinical practice but also a crucial strategy for enhancing patient survival rates. In comparison with traditional testing approaches, liquid biopsy offers the benefits of being less invasive and enabling repeated sampling. Through the examination of biological specimens that can be readily and repeatedly obtained from the patient's body, liquid biopsy can furnish information throughout the entire continuum of disease diagnosis, treatment, and follow-up prognosis. Consequently, it emerges as a highly prospective substitute for tissue samples in the minimally invasive, real-time, and comprehensive monitoring of tumors in clinical contexts. This article conducts a systematic review of the common liquid biopsy markers in the oncology field and their latest detection technologies. It encompasses detection schemes for non-blood samples such as cerebrospinal fluid and feces. Moreover, it proposes a novel framework for the precise management of the entire tumor process based on "multi-marker combination + full sample coverage". The article further deliberates on a series of challenges currently encountered in developing liquid biopsy into a mature clinical testing project. These challenges include the standardization of sample testing procedures, the establishment of standardized reporting systems, and how to strike a balance between the popularity of detection methods and cost control, with the aim of promoting the development of liquid biopsy in tumor early screening, treatment innovation, and extensive application. We anticipate constructing a full-chain system spanning from basic research to transformational production and clinical application. We aim to develop an integrated detection platform, establish standardized reporting procedures and a well-established regulatory mechanism, offer patients full-cycle precise management from diagnosis to rehabilitation, and ultimately convert cancer from an "incurable disease" into a "preventable and controllable" chronic disease.

 

Keywords: Liquid biopsy, Tumor biomarker, Minimal residual disease, Disease management, Review

 

Full Text:

PDF


References


BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263. doi: 10. 3322/caac.21834.

CHEN W Q, CHEN K X, HE Y T, et al. Expert consensus on liquid biopsy-based multi-cancer early detection (2025 edition). Chinese Journal of Oncology, 2025, 47(7): 558-574. doi: 10.3760/cma.j.cn112152-20250605-00257.

FAN L, WANG Z H, MA L X, et al. Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. Lancet Oncol, 2024, 25(2): 184-197. doi: 10.1016/S1470-2045(23)00579-X.

WU G, XU X, ZHANG H, et al. Liquid biopsy in biliary tract cancers: early diagnosis, precision therapy, and prognostic evaluation. Front Oncol, 2025, 15: 1705162. doi: 10.3389/fonc.2025.1705162.

SHEN F, ZAILAIE S A, CHIU B, et al. Liquid biopsy - a narrative review with an update on current US governmental clinical trials targeting immunotherapy. Future Sci OA, 2025, 11(1): 2527598. doi: 10.1080/ 20565623.2025.2527598.

AZIZI Z, ER URGANCI B, ACIKBAS I. Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse. World J Stem Cells, 2025, 17(12): 112990. doi: 10.4252/wjsc.v17.i12.112990.

TIAN C, XU X, WANG Y, et al. Development and Clinical Prospects of Techniques to Separate Circulating Tumor Cells from Peripheral Blood. Cancer Manag Res, 2020, 12: 7263-7275. doi: 10.2147/CMAR.S248380.

BAYOU N, HENRETTA S, MUNOZ-ARCOS L, et al. Quantitative HER2 profiling on circulating tumor cells using an EpCAM-independent platform in metastatic breast cancer. Cancer Cell Int, 2025, 25(1): 439. doi: 10.1186/s12935-025-04036-x.

COHEN E N, JAYACHANDRAN G, MOORE R G, et al. A Multi-Center Clinical Study to Harvest and Characterize Circulating Tumor Cells from Patients with Metastatic Breast Cancer Using the Parsortix((R)) PC1 System . Cancers (Basel) , 2022, 14(21): 5238. doi: 10.3390/cancers14215238.

AUGUSTSSON P, KARLSEN J T, SU H W, et al. Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping. Nat Commun, 2016, 7: 11556. doi: 10.1038/ncomms11556.

Di TRAPANI M, MANARESI N, MEDORO G. DEPArray system: An automatic image-based sorter for isolation of pure circulating tumor cells. Cytometry A, 2018, 93(12): 1260-1266. doi: 10.1002/cyto.a.23687.

LAWRENCE R, WATTERS M, DAVIES C R, et al. Circulating tumour cells for early detection of clinically relevant cancer. Nat Rev Clin Oncol, 2023, 20(7): 487-500. doi: 10.1038/s41571-023-00781-y.

DONATO C, SZCZERBA B M, SCHEIDMANN M C, et al. Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment. J Vis Exp, 2019, 147: e59677. doi: 10.3791/59677.

GUPTA R, ANDHARI S, NANDI S, et al. Inverse 3D 'lab-on-a-chip' polymeric microfilms for selective capture of circulating tumor cells from patients' blood. Lab Chip, 2025, 25(19): 4909-4919. doi: 10.1039/d4lc01105h.

GASCH C, BAUERNHOFER T, PICHLER M, et al. Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer. Clin Chem, 2013, 59(1): 252-260. doi: 10.1373/clinchem.2012.188557.

GKOUNTELA S, CASTRO-GINER F, SZCZERBA B M, et al. Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding. Cell, 2019, 176(1/2): 98-112.e114. doi: 10.1016/j.cell.2018.11.046.

CHENG Y H, CHEN Y C, LIN E, et al. Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells. Nat Commun, 2019, 10(1): 2163. doi: 10.1038/s41467-019-10122-2.

LOWES L E, ALLAN A L. Circulating Tumor Cells and Implications of the Epithelial-to-Mesenchymal Transition. Adv Clin Chem, 2018, 83: 121-181. doi: 10.1016/bs.acc.2017.10.004.

LEE D H, YOON W, LEE A, et al. Multi-biomarker panel prediction model for diagnosis of pancreatic cancer. J Hepatobiliary Pancreat Sci, 2023, 30(1): 122-132. doi: 10.1002/jhbp.986.

ANNAPRAGADA A V, NIKNAFS N, WHITE J R, et al. Genome-wide repeat landscapes in cancer and cell-free DNA. Sci Transl Med, 2024, 16(738): eadj9283. doi: 10.1126/scitranslmed.adj9283.

LIN C, LIU X, ZHENG B, et al. Liquid Biopsy, ctDNA Diagnosis through NGS. Life (Basel), 2021, 11(9): 890. doi: 10.3390/life11090890.

LI Y Z, KONG S N, LIU Y P, et al. Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC? J Clin Med, 2023, 12(4): 1438. doi: 10.3390/jcm12041438.

EMAUS M N, ANDERSON J L. Allelic discrimination between circulating tumor DNA fragments enabled by a multiplex-qPCR assay containing DNA-enriched magnetic ionic liquids. Anal Chim Acta, 2020, 1124: 184-193. doi: 10.1016/j.aca.2020.04.078.

SHEN S Y, SINGHANIA R, FEHRINGER G, et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature, 2018, 563(7732): 579-583. doi: 10.1038/s41586-018-0703-0.

KLEIN E A, RICHARDS D, COHN A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol, 2021, 32(9): 1167-1177. doi: 10. 1016/j.annonc.2021.05.806.

BAO H, WANG Z, MA X, et al. Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection. Mol Cancer, 2022, 21(1): 129. doi: 10.1186/s12943-022-01594-w.

XU J, WU W, WU C, et al. A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based EGFR p. T790M in non-small-cell lung cancer patients. Transl Lung Cancer Res, 2021, 10(10): 3888-3901. doi: 10.21037/tlcr-21-564.

ABRAHAM J, DOMENYUK V, PERDIGONES N, et al. Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors. Sci Rep, 2025, 15(1): 21173. doi: 10.1038/s41598-025-08986-0.

MAGEE D, DOMENYUK V, ABRAHAM J, et al. Characterization of Plasma Cell-Free DNA Variants as of Tumor or Clonal Hematopoiesis Origin in 16, 812 Advanced Cancer Patients. Clin Cancer Res, 2025, 31(13): 2710-2718. doi: 10.1158/1078-0432.CCR-24-3335.

ZHANG K, FU R, LIU R, et al. Circulating cell-free DNA-based multi-cancer early detection. Trends Cancer, 2024, 10(2): 161-174. doi: 10.1016/j.trecan.2023.08.010.

HE Q, LIU L, WANG Y, et al. miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain. Mol Pain, 2022, 18: 17448069221127811. doi: 10.1177/17448069221127811.

HO P T B, CLARK I M, LE L T T. MicroRNA-Based Diagnosis and Therapy. Int J Mol Sci, 2022, 23(13): 7167. doi: 10.3390/ijms23137167.

INETAS-YENGIN G, OMEROGLU-ULU Z, SAHIN F, et al. Evaluation of Plasma-Derived Cell-Free RNA isolation methods using PCR-Based quantification. Mol Biol Rep, 2026, 53(1): 249. doi: 10.1007/s11033-025-11410-5.

AMIN M, ISLAM F, GOPALAN V, et al. Detection and Quantification of MicroRNAs in Esophageal Adenocarcinoma. Methods Mol Biol, 2018, 1756: 257-268. doi: 10.1007/978-1-4939-7734-5_22.

ZHANG F, GUO J, ZHANG Z, et al. Application of engineered extracellular vesicles for targeted tumor therapy. J Biomed Sci, 2022, 29(1): 14. doi: 10.1186/s12929-022-00798-y.


Refbacks

  • There are currently no refbacks.