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      液体活检在非小细胞肺癌中的临床应用进展 Translated title: Advances in Clinical Application of Liquid Biopsy in Non-small Cell Lung Cancer

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          Abstract

          肺癌是我国发病率最高的癌症,也是癌症患者死亡的首要病因。其中,约85%是非小细胞肺癌(non-small cell lung cancer, NSCLC)。肺癌患者的诊断方法和治疗措施一直是重中之重。近年来,随着分子生物学检测技术的快速进步以及精准治疗和个体化治疗的发展,液体活检因其具有传统侵入性活检所不具备的优点而成为关注的焦点,如安全、便捷、重复性、低创伤性等。液体活检作为一种新兴技术,其检测对象主要包括外周血中的循环肿瘤DNA(circulating tumor DNA, ctDNA)、循环肿瘤细胞(circulating tumor cells, CTCs)、外泌体等。本文将对ctDNA、CTCs和外泌体的检测及其在NSCLC患者中的临床应用作一简要综述。

          Translated abstract

          Lung cancer, with the highest incidence in China, is the leading cause of death in cancer patients. Of these, about 85% are patients with non-small cell lung cancer (NSCLC). Therefore, the diagnosis and treatment of patients with lung cancer have always been a top priority nowadays. Fluid biopsy has many advantages, such as safety, convenience, repeatability, low trauma and so on, which are not available in traditional invasive biopsy. In recent years, with the rapid progress of molecular biological detection technology, fluid biopsy, as a new technology, has become the focus of attention. What's more, it contributes to the development of precision treatment and individualized treatment of lung cancer. Liquid biopsy mainly detects circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and exosomes in peripheral blood. We will make an introduce to the detection and clinical applications of ctDNA, CTCs and exocrine in this article, in order that it can provide insights into future clinical treatment for NSCLC.

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          Most cited references39

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Detection of circulating tumor DNA in early- and late-stage human malignancies.

            The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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              Membrane vesicles as conveyors of immune responses.

              In multicellular organisms, communication between cells mainly involves the secretion of proteins that then bind to receptors on neighbouring cells. But another mode of intercellular communication - the release of membrane vesicles - has recently become the subject of increasing interest. Membrane vesicles are complex structures composed of a lipid bilayer that contains transmembrane proteins and encloses soluble hydrophilic components derived from the cytosol of the donor cell. These vesicles have been shown to affect the physiology of neighbouring recipient cells in various ways, from inducing intracellular signalling following binding to receptors to conferring new properties after the acquisition of new receptors, enzymes or even genetic material from the vesicles. This Review focuses on the role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells.
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                Author and article information

                Contributors
                Journal
                Zhongguo Fei Ai Za Zhi
                Zhongguo Fei Ai Za Zhi
                ZGFAZZ
                Chinese Journal of Lung Cancer
                中国肺癌杂志编辑部 (天津市和平区南京路228号300020 )
                1009-3419
                1999-6187
                20 October 2021
                : 24
                : 10
                : 723-728
                Affiliations
                [ ] 116000 大连,大连医科大学附属第二医院肿瘤科 Department of Oncology, The Second Hospital of Dalian Medical University, Dalian 116000, China
                Author notes
                陈骏, Jun CHEN, E-mail: chenjundl@ 123456vip.sina.com
                Article
                zgfazz-24-10-723
                10.3779/j.issn.1009-3419.2021.102.33
                8560984
                34696544
                0ea98621-5222-4fba-b953-fd5ec7dadcef
                版权所有©《中国肺癌杂志》编辑部2021Copyright ©2021 Chinese Journal of Lung Cancer. All rights reserved.

                This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) License. See: https://creativecommons.org/licenses/by/3.0/.

                History
                : 12 June 2021
                : 12 August 2021
                : 30 August 2021
                Categories
                综述
                Review

                肺肿瘤,液体活检,循环肿瘤dna,循环肿瘤细胞,外泌体,lung neoplasms,liquid biopsy,circulating tumor dna,circulating tumor cells,exosomes

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