Liquid Biopsy and Tumor Heterogeneity in Metastatic Solid Tumors: the Potentiality of Blood Samples

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2020 May 29

PMID 32460897

Citations 130

Authors

Marco Russano

Andrea Napolitano

Giulia Ribelli

Michele Iuliani

Sonia Simonetti

Fabrizio Citarella

Francesco Pantano

Emanuela DellAquila

Cecilia Anesi

Nicola Silvestris

Antonella Argentiero

Antonio Giovanni Solimando

Bruno Vincenzi

Giuseppe Tonini

Daniele Santini

Affiliations

Soon will be listed here.

Abstract

In a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers. Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field.Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Samples can be obtained from blood and most other bodily fluids. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids.In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients.

Citing Articles

Plasma treatment can efficiently increase the attachment of pancreatic circulatory tumor cells to the surface.

Mahdian S, Mahmoudi-Aznaveh A, Mousavi S, Larijani B, Azizi Z, Javar H Discov Oncol. 2025; 16(1):222.

PMID: 39982607 PMC: 11845332. DOI: 10.1007/s12672-025-01988-4.

Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients.

Ruglioni M, Petrini I, Crucitta S, Sbrana A, Luculli G, Sadeghi Gol L Transl Oncol. 2024; 52:102228.

PMID: 39709717 PMC: 11832947. DOI: 10.1016/j.tranon.2024.102228.

Emerging advanced approaches for liquid biopsy: nucleic acid assays of extracellular vesicles.

Wang D, Shen Y, Qian H, Jiang J, Xu W Theranostics. 2024; 14(19):7309-7332.

PMID: 39659566 PMC: 11626945. DOI: 10.7150/thno.102437.

Making the effect visible - OX40 targeting nanobodies for imaging of activated T cells.

Frecot D, Blaess S, Wagner T, Kaiser P, Traenkle B, Fandrich M Front Immunol. 2024; 15:1480091.

PMID: 39474429 PMC: 11518761. DOI: 10.3389/fimmu.2024.1480091.

DNA demethylation triggers cell free DNA release in colorectal cancer cells.

Pessei V, Macagno M, Mariella E, Congiusta N, Battaglieri V, Battuello P Genome Med. 2024; 16(1):118.

PMID: 39385243 PMC: 11462661. DOI: 10.1186/s13073-024-01386-5.

References

Sorber L, Zwaenepoel K, Deschoolmeester V, Van Schil P, Van Meerbeeck J, Lardon F . Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients. Lung Cancer. 2016; 107:100-107. DOI: 10.1016/j.lungcan.2016.04.026. View

Feng H, Qin Z, Zhang X . Opportunities and methods for studying alternative splicing in cancer with RNA-Seq. Cancer Lett. 2012; 340(2):179-91. DOI: 10.1016/j.canlet.2012.11.010. View

Denis J, Patroni A, Guillerm E, Pepin D, Benali-Furet N, Wechsler J . Droplet digital PCR of circulating tumor cells from colorectal cancer patients can predict KRAS mutations before surgery. Mol Oncol. 2016; 10(8):1221-31. PMC: 5423194. DOI: 10.1016/j.molonc.2016.05.009. View

Douillard J, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G . Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014; 9(9):1345-53. PMC: 4224589. DOI: 10.1097/JTO.0000000000000263. View

Wang S, Jiang J, Zhang C, Zhang X, Wang C . Serum lincRNA-p21 expression in primary liver diseases and liver metastatic diseases. Pathol Res Pract. 2019; 215(4):779-783. DOI: 10.1016/j.prp.2019.01.014. View

Aceto N, Bardia A, Miyamoto D, Donaldson M, Wittner B, Spencer J . Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014; 158(5):1110-1122. PMC: 4149753. DOI: 10.1016/j.cell.2014.07.013. View

Yuwen D, Sheng B, Liu J, Wenyu W, Shu Y . MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer. Eur Rev Med Pharmacol Sci. 2017; 21(11):2650-2658. View

Ma R, Jiang T, Kang X . Circulating microRNAs in cancer: origin, function and application. J Exp Clin Cancer Res. 2012; 31:38. PMC: 3431991. DOI: 10.1186/1756-9966-31-38. View

Gros A, Parkhurst M, Tran E, Pasetto A, Robbins P, Ilyas S . Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016; 22(4):433-8. PMC: 7446107. DOI: 10.1038/nm.4051. View

10.

Gong Y, Mao J, Wu D, Wang X, Li L, Zhu L . Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6. Cancer Cell Int. 2018; 18:116. PMC: 6090603. DOI: 10.1186/s12935-018-0602-3. View

11.

Subrahmanyam P, Dong Z, Gusenleitner D, Giobbie-Hurder A, Severgnini M, Zhou J . Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients. J Immunother Cancer. 2018; 6(1):18. PMC: 5840795. DOI: 10.1186/s40425-018-0328-8. View

12.

Arakawa A, Vollmer S, Tietze J, Galinski A, Heppt M, Burdek M . Clonality of CD4 Blood T Cells Predicts Longer Survival With CTLA4 or PD-1 Checkpoint Inhibition in Advanced Melanoma. Front Immunol. 2019; 10:1336. PMC: 6591437. DOI: 10.3389/fimmu.2019.01336. View

13.

Wei F, Ma C, Zhou T, Dong X, Luo Q, Geng L . Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p. Mol Cancer. 2017; 16(1):132. PMC: 5526308. DOI: 10.1186/s12943-017-0694-8. View

14.

Sade-Feldman M, Kanterman J, Klieger Y, Ish-Shalom E, Olga M, Saragovi A . Clinical Significance of Circulating CD33+CD11b+HLA-DR- Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab. Clin Cancer Res. 2016; 22(23):5661-5672. DOI: 10.1158/1078-0432.CCR-15-3104. View

15.

Qu F, Xie W, Nakabayashi M, Zhang H, Jeong S, Wang X . Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer. Clin Cancer Res. 2016; 23(3):726-734. PMC: 5675562. DOI: 10.1158/1078-0432.CCR-16-1070. View

16.

Kartha R, Subramanian S . Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet. 2014; 5:8. PMC: 3906566. DOI: 10.3389/fgene.2014.00008. View

17.

Cui C, Tian X, Wu J, Zhang C, Tan Q, Guan X . T cell receptor β-chain repertoire analysis of tumor-infiltrating lymphocytes in pancreatic cancer. Cancer Sci. 2018; 110(1):61-71. PMC: 6317932. DOI: 10.1111/cas.13877. View

18.

Mazel M, Jacot W, Pantel K, Bartkowiak K, Topart D, Cayrefourcq L . Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol. 2015; 9(9):1773-82. PMC: 5528721. DOI: 10.1016/j.molonc.2015.05.009. View

19.

Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F . Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial. JAMA Oncol. 2015; 1(2):149-57. DOI: 10.1001/jamaoncol.2014.257. View

20.

Ye C, Shen Z, Wang B, Li Y, Li T, Yang Y . A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit. J Exp Clin Cancer Res. 2016; 35(1):187. PMC: 5135755. DOI: 10.1186/s13046-016-0467-z. View