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 Table of Contents  
EDITORIAL
Year : 2018  |  Volume : 2  |  Issue : 3  |  Page : 45-46

Liquid biopsy in oncology practice


Department of Radiotherapy, HCG Panda Cancer Hospital, Cuttack, Odisha, India

Date of Web Publication21-Sep-2018

Correspondence Address:
Dr. Tapan Kumar Sahoo
Department of Radiotherapy, HCG Panda Cancer Hospital, Cuttack, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_32_18

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How to cite this article:
Sahoo TK. Liquid biopsy in oncology practice. Oncol J India 2018;2:45-6

How to cite this URL:
Sahoo TK. Liquid biopsy in oncology practice. Oncol J India [serial online] 2018 [cited 2018 Nov 19];2:45-6. Available from: http://www.ojionline.org/text.asp?2018/2/3/45/241844



Malignancy is one of the major causes of morbidity and mortality worldwide due to advanced stage of presentation at the time of diagnosis. Instead of development in different treatment modalities, the survival outcome is still not significantly improved. Metastatic disease still remains incurable in almost all the cases. Therefore, the current therapeutic strategies allow successful treatment of the disease if it is detected early. However, early detection of cancer and selection of targeted therapies based on improved understanding of the genetic basis of disease may increase the outcome of the disease.

A sequential series of alterations in specific cancer genes affecting the function of certain pathways over several decades leads to the development of cancer, and the majority of cancers are not detected in the first 90% of the cancers' lifetimes. Development in advance knowledge about the involvement of driver genes and the pathways causing cancer arises the question of utility of liquid biopsies as a novel strategy for clinical practice in the field of malignancies.[1]


  Need of Liquid Biopsy Top


Biopsy is a surgical procedure with more risk than taking a blood sample, and further biopsies during the treatment are difficult due to risk to a patient. Tumors show intratumoral heterogeneity and clones within the tumor may arise showing different behavior.[2] The choice of biomarkers is crucial for early detection of cancer due to lack of specificity and sensitivity, lower concentration in early stages in comparison to late stages, and masked by other comorbidities such as chronic inflammatory diseases, as well as by the accumulation of cancer-related mutations with age in healthy individuals. Nowadays, the concept of liquid biopsy introduces to the clinical practice to overcome this pitfall.


  Concept of Liquid Biopsy Top


The analysis of detectable tumor cells and tumor-derived products in the blood and other body fluids introduces the concept of liquid biopsy. Liquid biopsy has the potential to provide information about cancers without invasive biopsy, using circulating biomarkers. While protein-based tumor markers have been used in routine pathology for many years, the ability to detect mutations in circulating DNA is relatively new and poised to enter clinical practice. Circulating tumor cells (CTCs), circulating cell-free tumor DNA (ctDNA), circulating microRNA (miRNA), long noncoding RNAs, tumor-derived exosomes, and tumor-educated platelets are the analytes for liquid biopsy.[3],[4] CTCs are present in the peripheral blood of patients with majority of advanced cancer, but there is uncertainty around the sensitivity of CTCs in low-volume disease in comparison with ctDNA and miRNA. ctDNA levels that reflect tumor load with increased levels can be found in premalignancy, and it permits the detection of mutations to guide therapy and altered gene methylation. miRNA signatures are providing promising results for cancer detection although their ability to predict response to therapy is uncertain.[3]

Examination of molecular characteristics of the tumor by these analytes is likely to greatly influence personalized management of cancer patients. It not only be a modality for early detection, diagnosis, response evaluation, disease progression, and emerging therapy resistance mechanisms but also assess tumor heterogeneity and evolution in real time.[2]


  Liquid Biopsy in Early-Stage Cancers Top


Early detection of small tumors, improved risk assessment, and monitoring of minimal residual disease (MRD) are the three clinical applications of liquid biopsy in early-stage cancer patients. These three applications should be implemented in future clinical trials to cure cancer patients before overt metastasis. Liquid biopsies have to meet the enormous biological and technical challenges to detect precursor lesions or early cancer stages with increased sensitivity and specificity. Proximal sampling should be done with the analysis of other body fluids close to the organ at high risk of malignant transformation in individual at high risk to extend systemic screening approaches. Profiling of the resected tumor with curative intent should be done for the design of personalized assay panels useful for monitoring approaches. Searching for mutations, somatic copy number alterations (SCNAs), or analyses of methylation and chromatin patterns should be done. Monitoring of MRD in early-stage cancers is a challenging issue due to low concentration of ctDNA and other analytes in the blood. However, results of few studies demonstrate the power of ctDNA analysis in predicting MRD in lung, colon, and breast cancer patients.[3],[5],[6]

Monitoring of response to therapy with serial circulating cell free DNA (cfDNA) analyses during treatment may detect the emergence of resistance-associated mutations in early phase and will guide the clinicians for precision of therapy. Goodall et al. detected mutations that reverted germline and somatic DNA repair mutations back in frame in patients treated with the poly-ADP-ribose polymerase inhibitor olaparib.[7] Siravegna et al. on ctDNA analysis observed the emergence of KRAS mutations with disease progression during anti-epidermal growth factor receptor (anti-EGFR) therapy for colorectal cancer. KRAS-mutant clones decline in number during withdrawal of therapy, suggesting rechallenge with anti-EGFR therapy after a period of therapy withdrawal, and provide a rationale for interventional clinical studies with cfDNA-driven decisions.[8] Nonsmall cell lung cancer patients can be started with third-generation tyrosine kinase inhibitors without rebiopsy through cfDNA analysis with EGFR T790M mutation testing using the Cobas® EGFR Mutation Test v2.[3]


  Address of Critical Questions Top


Tumor size, clinical signs, detectable by imaging, favorable to unfavorable features on biopsy, certainty for established tumor markers, knowledge of genes to be targeted and established driver genes, certainty about release of tumor DNA into the circulation, tumor heterogeneity, applicable plasma DNA technologies, option of proximal sampling, option to design personalized assays, expected variant allelic frequency of somatic mutations in blood, presence of potentially confounding mutations and clones, detection of SCNAs, and no availability of established clinical guidelines are the such critical questions.[1]


  Negative Issues Top


In case of small cancers, particularly breast cancer with favorable molecular features, the early detection of cancer by screening may not progress to large tumors within the lifetime of the patient, resulting overdiagnosis by screening. Furthermore, these tumors can be treated effectively at clinical presentation with excellent prognosis offering little benefit to early detection. Till date, early screening did not prove to be a lifesaver in thyroid, prostate, and breast malignancies.

Sensitivity of liquid biopsy-based approaches may be improved by adding classical biochemical cancer markers and/or imaging techniques. Due to inadequate knowledge on biology of carcinogenesis, the development of highly sensitive screening tests is not available till date. There is no 100% sensitivity and specificity to achieve early detection by liquid biopsy tests. However, a test with certain percentage of capability for early detection of cancer could have a great impact on the life of many individuals. Lack of sufficient clinical and technical validation and clinical utility is the major drawback of liquid biopsy.



 
  References Top

1.
Heitzer E, Perakis S, Geigl JB, Speicher MR. The potential of liquid biopsies for the early detection of cancer. NPJ Precis Oncol 2017;1:36.  Back to cited text no. 1
    
2.
Cree IA. Liquid biopsy for cancer patients: Principles and practice. Pathogenesis 2015;2:1-4.  Back to cited text no. 2
    
3.
Babayan A, Pantel K. Advances in liquid biopsy approaches for early detection and monitoring of cancer. Genome Med 2018;10:21.  Back to cited text no. 3
[PUBMED]    
4.
Sahoo TK. Screening for early detection of cancer – Hope for cure. Oncol J India 2018;2:23-4.  Back to cited text no. 4
  [Full text]  
5.
Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 2017;545:446-51.  Back to cited text no. 5
[PUBMED]    
6.
Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov 2017;7:1394-403.  Back to cited text no. 6
    
7.
Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, et al. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov 2017;7:1006-17.  Back to cited text no. 7
    
8.
Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med 2015;21:795-801.  Back to cited text no. 8
    




 

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