Correlation between Plasma DNA and Tumor Status in an Animal Model

Sueoka‐Aragane, Naoko; Sato, Akemi; Kobayashi, Nozomu; Ide, Masaru; Yokoo, Masako; Nagano, Yumi; Sueoka, Eisaburo; Okada, Seiji; Kimura, Shinya

doi:10.1371/journal.pone.0111881

Cited by 15 publications

(18 citation statements)

References 41 publications

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“…(16,17) Recent data from animal studies in our laboratory indicate that the amount of tumorderived DNA is related to aspects of tumor progression, such as metastasis. (18) The effects of EGFR-TKI, such as best response, duration of treatment and progression-free survival, were not correlated with detection of T790M in plasma. In contrast, T790M in plasma was frequently observed in smokers, males and patients with exon 19 deletions.…”

Section: Discussionmentioning

confidence: 97%

“…Tumor‐derived DNA has been thought to be released into peripheral blood after necrosis and/or apoptosis, but mainly necrosis, and it has been assumed to be related to tumor burden, stage and cellular turnover . Recent data from animal studies in our laboratory indicate that the amount of tumor‐derived DNA is related to aspects of tumor progression, such as metastasis …”

Section: Discussionmentioning

confidence: 99%

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Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study

et al. 2016

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Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. EGFR T790M has been observed in half of lung cancer patients who have acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Effectiveness of monitoring T790M via plasma DNA during treatment with EGFR-TKI has not been established as an alternative to re-biopsy. This was a prospective multicenter observational study involving non-small cell lung cancer patients carrying EGFR L858R or exon 19 deletions, treated with EGFR-TKI. The primary objective was to determine whether T790M could be detected using plasma DNA in patients with progressive disease (PD). T790M was examined using the mutation-biased PCR and quenching probe (MBP-QP) method, a sensitive, fully-automated system developed in our laboratory. Eighty-nine non-small cell lung cancer patients were enrolled from seven hospitals in Japan. Sequential examinations revealed T790M in plasma DNA among 40% of patients who developed PD. Activating mutations, such as L858R and exon 19 deletions, were detected in 40% of patients using plasma DNA, and either T790M or activating mutations were observed in 62%. Dividing into four periods (before PD, at PD, at discontinuation of EGFR-TKI and subsequently), T790M was detected in 10, 19, 24 and 27% of patients, respectively. Smokers, males, patients having exon 19 deletions and patients who developed new lesions evidenced significantly frequent presence of T790M in plasma DNA. Monitoring T790M with plasma DNA using MBP-QP reflects the clinical course of lung cancer patients treated with EGFR-TKI. Detection of T790M with plasma DNA was correlated with EGFR mutation type, exon 19 deletions and tumor progression. Re-biopsy could be performed only in 14% of PD cases, suggesting difficulty in obtaining re-biopsy specimens in practice. Monitoring T790M with plasma DNA reflects the clinical course, and is potentially useful in designing strategies for subsequent treatment.C ompanion diagnostics has seen growing importance, especially for molecular targeted therapy such as EGFR tyrosine kinase inhibitors (EGFR-TKI) in lung cancer. Recently, a second generation EGFR-TKI, afatinib, evidenced a potent anti-cancer effect against lung cancer cells harboring T790M,(1) but the anti-cancer effect in a phase 2b ⁄ 3 randomized trial was unsatisfactory considering the results of preclinical studies.(2) Because examination of biomarkers related to acquired resistance to EGFR-TKI was not performed in that trial, it is speculated that the patients included those with cancers possessing various mechanisms of acquired resistance to EGFR-TKI. Recently, third generation EGFR-TKI, such as AZD9291 and CO-1686, have shown potent anti-cancer effects in T790M positive non-small cell lung cancer patients. (3,4) Considering this evidence, examination of biomarkers is indispensable for accurate assessment of anti-cancer effects, and timely monitoring of genetic alterations is necessary for determining appropriate treatment.The use of circulating free DNA to detec...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study

et al. 2016

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“…[9][10][11][12][13][14][15] The discovery of a relationship between epidermal growth factor receptor (EGFR)activating mutations and EGFR-tyrosine kinase inhibitors (TKI) has taken the treatment of patients with EGFR mutations into an era of precision medicine. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] The 2009…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a novel saliva‐based epidermal growth factor receptor mutation detection for lung cancer: A pilot study

Hao

Fang

et al. 2016

Thoracic Cancer

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BackgroundThis article describes a pilot study evaluating a novel liquid biopsy system for non‐small cell lung cancer (NSCLC) patients. The electric field‐induced release and measurement (EFIRM) method utilizes an electrochemical biosensor for detecting oncogenic mutations in biofluids.MethodsSaliva and plasma of 17 patients were collected from three cancer centers prior to and after surgical resection. The EFIRM method was then applied to the collected samples to assay for exon 19 deletion and p.L858 mutations. EFIRM results were compared with cobas results of exon 19 deletion and p.L858 mutation detection in cancer tissues.ResultsThe EFIRM method was found to detect exon 19 deletion with an area under the curve (AUC) of 1.0 in both saliva and plasma samples in lung cancer patients. For L858R mutation detection, the AUC of saliva was 1.0, while the AUC of plasma was 0.98. Strong correlations were also found between presurgery and post‐surgery samples for both saliva (0.86 for exon 19 and 0.98 for L858R) and plasma (0.73 for exon 19 and 0.94 for L858R).ConclusionOur study demonstrates the feasibility of utilizing EFIRM to rapidly, non‐invasively, and conveniently detect epidermal growth factor receptor mutations in the saliva of patients with NSCLC, with results corresponding perfectly with the results of cobas tissue genotyping.

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Section: Introductionmentioning

confidence: 99%

“…Since that discovery, increased exDNA levels in human blood repeatedly have been found to be a hallmark of metastatic cancer (41)(42)(43)(44)(45)(46)(47). Suggested mechanisms have included DNA release from actively dividing tumor cells (42), tumor lysis, apoptosis, and necrosis (28,32), but whether these phenomena underlie changes in exDNA levels in cancer patients has remained unclear (41)(42)(43)(44)(45)(46). Based on the logical presumption that such "circulating DNA" in cancer patients is derived from dead tumor cells (2,43), interest in the potential for using the exDNA sequences as a "liquid biopsy" for diagnostic purposes has been high and the phenomenon has been documented in hundreds of papers (32,(48)(49)(50).…”

Section: Introductionmentioning

confidence: 99%

Extracellular DNA: A Bridge to Cancer

2015

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DNase I is a secreted enzyme whose function has been presumed to control "waste management" in the human system, by degrading DNA that leaks from dead and dying cells. Emerging studies have instead yielded evidence that DNase I plays a central role in newly defined dynamics of immune and autoimmune diseases, as well as cancer and vascular disorders, including thrombosis. Cancer cells have been reported to be associated with distinctive extracellular structures that facilitate aggregation and implantation. The fact that DNA is a component of such structures and that it plays a role in cancer development is illustrated by direct evidence: DNase I added to tumor cells eliminates the structures and inhibits tumorigenicity of some cancer cell lines. DNase I injected into experimental animals, moreover, results in significant inhibition of metastasis. Despite independent observations of such phenomena in diverse cancers for over 50 years, the potential for using DNase I as a clinical tool to prevent or treat cancer remains unexplored. The discovery of neutrophil extracellular traps has yielded a conceptual framework for interpreting how extracellular DNA may function in cancer development and why it may prove to be an important clinical target in stopping cancer outside the cell. Cancer Res; 75(20);

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Correlation between Plasma DNA and Tumor Status in an Animal Model

Cited by 15 publications

References 41 publications

Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study

Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study

Evaluation of a novel saliva‐based epidermal growth factor receptor mutation detection for lung cancer: A pilot study

Extracellular DNA: A Bridge to Cancer

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