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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 4  |  Page : 863-864

Expanding opportunities in precision oncology

Department of Medical Oncology, Apollo Hospitals, Chennai, Tamil Nadu, India

Date of Submission28-Oct-2020
Date of Decision09-Dec-2020
Date of Acceptance09-Dec-2020
Date of Web Publication25-Dec-2020

Correspondence Address:
T Raja
Apollo Hospitals, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_340_20

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How to cite this article:
Raja T. Expanding opportunities in precision oncology. Cancer Res Stat Treat 2020;3:863-4

How to cite this URL:
Raja T. Expanding opportunities in precision oncology. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jan 18];3:863-4. Available from: https://www.crstonline.com/text.asp?2020/3/4/863/305005

Liquid biopsy is a minimally invasive procedure that can circumvent the challenges of surgical and core biopsies. It plays a supportive role in situations that require serial monitoring, especially when a tissue biopsy is not possible. The liquid biopsy also offers us the unique advantage of the ease of collection and analysis of different types of bodily fluids. Tumors such as non-small-cell lung cancer (NSCLC) are generally heterogeneous and comprise various subclones. Some subclones outgrow the others due to therapeutic stress caused, especially by the targeted drugs, which can cause changes in the tumor microenvironment leading to disease progression/metastasis. These changes can dynamically modify the genomic landscape of the tumor. One of the advantages of liquid biopsies is that it better represents the genomic heterogeneity of the tumors.[1],[2],[3],[4]

However, the liquid biopsy also has certain limitations. The detection of circulating tumor DNA (ctDNA) requires highly sensitive techniques as traditional techniques such as Sanger sequencing and pyrosequencing cannot be used because of the low fraction and high fragmentation rates of ctDNA. The lack of availability of these highly sensitive tests in the laboratories poses a practical challenge. Further, liquid biopsy requires highly specialized and specific sample processing and handling and does not provide information about the tumor histology or morphological changes like small cell lung cancer transformation, which is one of the acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance mechanisms.[1],[5],[6],[7]

The usefulness of ctDNA mutation analysis translating into a noninvasive approach for the detection of targetable mutations causing resistance to therapy is a welcome advance. In a study of patients with lung cancer by Rijavec et al., the analysis of cell-free DNA (cfDNA) showed the appearance of the T790M EGFR mutation following gefitinib treatment, supporting the hypothesis of treatment-related selective pressure. Following this, Thress et al. analyzed the cfDNA from 15 patients harboring the EGFR T790M mutation and identified the C797S EGFR mutation as a novel acquired resistance mechanism to AZD9291.[8],[9],[10]

In the last issue of the Journal, through their commendable study, Chougule et al.[11],[12] have shown that the concordance for mutation detection of the formalin-fixed and paraffin-embedded tissue samples with plasma was 64% and that with the other bodily fluids was 100%. More hearteningly, it was possible to detect the exon 20 T790M resistance mutation in the plasma and other bodily fluids at progression. This highlights the increasing number of various applications of liquid biopsy in the diagnosis and treatment decision-making of patients with NSCLC. Moreover, the minimally invasive nature and the low cost of liquid biopsy allow for repeated testing, making it a very useful tool in clinical practice.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Chang S, Hur JY, Choi YL, Lee CH, Kim WS. Current status and future perspectives of liquid biopsy in non-small cell lung cancer. J Pathol Transl Med 2020;54:204-12.  Back to cited text no. 1
Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 2017;14:531-48.  Back to cited text no. 2
Heydt C, Michels S, Thress KS, Bergner S, Wolf J, Buettner R, et al. Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance. Oncotarget 2018;9:15418-34.  Back to cited text no. 3
Sholl LM, Aisner DL, Allen TC, Beasley MB, Cagle PT, Capelozzi VL, et al. Liquid biopsy in lung cancer: A Perspective from members of the pulmonary pathology society. Arch Pathol Lab Med 2016;140:825-9.  Back to cited text no. 4
Heitzer E, Auer M, Hoffmann EM, Pichler M, Gasch C, Ulz P, et al. Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer. Int J Cancer 2013;133:346-56.  Back to cited text no. 5
Lo YM, Chan KC, Sun H, Chen EZ, Jiang P, Lun FM, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010;2:61ra91.  Back to cited text no. 6
Hench IB, Hench J, Tolnay M. Liquid biopsy in clinical management of breast, lung, and colorectal cancer. Front Med (Lausanne) 2018;5:9.  Back to cited text no. 7
Rijavec E, Coco S, Genova C, Rossi G, Longo L, Grossi F, et al. Liquid biopsy in non-small cell lung cancer: Highlights and challenges. Cancers (Basel) 2019;12:17.  Back to cited text no. 8
Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 2015;21:560-2.  Back to cited text no. 9
Chabon JJ, Simmons AD, Lovejoy AF, Esfahani MS, Newman AM, Haringsma HJ, et al. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun 2016;7:11815.  Back to cited text no. 10
Chougule A, Pange P, Kale S, Jagtap V, Nambiar K, Nikam A, et al. Concordance of epidermal growth factor receptor mutation detection in bodily fluids other than blood with tissue biopsy: A retrospective analysis. Cancer Res Stat Treat 2020;3:475-80.  Back to cited text no. 11
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Addeo A, Friedlaender A. Circulating tumor DNA in non-small-cell lung cancer: A step beyond blood. Cancer Res Stat Treat 2020;3:577-9.  Back to cited text no. 12
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