Free DNA and Carcinoembryonic Antigen Serum Levels: An Important Combination for Diagnosis of Colorectal Cancer

Flamini, Emanuela; Mercatali, Laura; Nanni, Oriana; Calistri, Daniele; Nunziatini, Roberta; Zoli, Wainer; Rosetti, Paola; Gardini, Nice; Lattuneddu, Arturo; Verdecchia, Giorgio Maria; Amadori, Dino

doi:10.1158/1078-0432.ccr-06-1931

Cited by 112 publications

(84 citation statements)

References 23 publications

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“…In general, the levels are higher in mCRC patients than in healthy controls, as shown in Table 1 [15,20,47,58,[63][64][65][66][67][68][69][70][71][72]; and the levels have some correlation to stage as reported in a limited number of studies [15,41,68,73] in primary CRC. These findings give important biological information, and researchers suggest that cfDNA has potential as a diagnostic or screening tool; a potential that is currently being investigated by several groups.…”

Section: Methodsmentioning

confidence: 71%

“…It is therefore relevant to analyze the relation between cfDNA and CEA. As illustrated from the summary in Table 2, there is considerable variation in the measures, methods and parameter used to compare or combine the information from CEA and cfDNA analysis [15,20,32,33,39,41,[65][66][67][68][69][70][71][72][81][82][83]. The table includes studies identified by a systematic literature search of circulating DNA in CRC (all stages) as illustrated by Supplementary Figure 1.…”

Section: Methodsmentioning

confidence: 99%

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Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Spindler

2016

Acta Oncologica

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Background: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment. This review aims to present the current literature which has specifically reported data on the potential utility of cfDNA and on tumor-specific mutations in metastatic colorectal cancer (mCRC). Method: Methodological, biological and clinical aspects are discussed based on the most recent development in this specific setting, and eligible studies were identified by systematic literature searched from Pubmed and EMBASE in addition to conference papers and communications. Results: The literature regarding cfDNA in CRC is broad and heterogeneous concerning aims, nomenclature, methods, cohorts and clinical endpoints and consequently difficult to include in a single systematic search. However, the available data underline a strong clinical value of measuring both total cfDNA levels and tumor-specific mutations in the plasma of patients with mCRC, pre-and during systemic therapy. Conclusion: This paper had gathered the most recent literature on several aspects of cfDNA in mCRC, including methodological, biological and clinical aspects, and discussed the large clinical potential in this specific setting, which needs to be validated in carefully designed prospective studies in statistically relevant cohorts.

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Section: Methodsmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Spindler

2016

Acta Oncologica

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“…Figure 2D shows the effect of 3 different concentrations of soluble CEA (sCEA) ranging from 0.2 to 5 mg/mL, with 5 mg/mL representing a level above that typically found in the serum of cancer patients with CEA positive tumors. 68,69 The concentrations of MEDI-565 for half-maximal lysis of target cells expressing CEA were 1.5 ng/mL for MEDI-565 alone, 4.0 ng/mL of MEDI-565 for 0.2 mg/mL of sCEA, 1.3 ng/ mL of MEDI-565 for 1.0 mg/mL of sCEA and 2.1 ng/mL of MEDI-565 for 5.0 mg/mL of sCEA (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

“…Although sCEA competitively inhibited binding of MEDI-565 to surface CEA, MEDI-565 was still able to kill tumor cells in vitro in a manner that was insensitive to soluble CEA at concentrations (5 mg/mL) that are above those typically found in the plasma of cancer patients, 68,69 and in vivo in animals bearing human tumors expressing and shedding CEA. This suggests that CEA shed into the blood of cancer patients or into the local tumor microenvironment may not represent a significant pharmacological sink that would negatively affect the activity of MEDI-565.…”

Section: Discussionmentioning

confidence: 96%

CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas

Oberst¹,

Fuhrmann²,

Mulgrew³

et al. 2014

mAbs

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A Hammond (2014) CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas, mAbs, 6:6, 1571-1584, DOI: 10.4161/19420862.2014 To link to this article: https://doi.org/10. 4161/19420862.2014 Individual or combinations of somatic mutations found in genes from colorectal cancers can redirect the effects of chemotherapy and targeted agents on cancer cell survival and, consequently, on clinical outcome. Novel therapeutics with mechanisms of action that are independent of mutational status would therefore fulfill a current unmet clinical need. Here the CEA and CD3 bispecific single-chain antibody MEDI-565 (also known as MT111 and AMG 211) was evaluated for its ability to activate T cells both in vitro and in vivo and to kill human tumor cell lines harboring various somatic mutations commonly found in colorectal cancers. MEDI-565 specifically bound to normal and malignant tissues in a CEA-specific manner, and only killed CEA positive cells. The BiTE Ò antibody construct mediated T cell-directed killing of CEA positive tumor cells within 6 hours, at low effector-to-target ratios which were independent of high concentrations of soluble CEA. The potency of in vitro lysis was dependent on CEA antigen density but independent of the mutational status in cancer cell lines. Importantly, individual or combinations of mutated KRAS and BRAF oncogenes, activating PI3KCA mutations, loss of PTEN expression, and loss-of-function mutations in TP53 did not reduce the activity in vitro. MEDI-565 also prevented growth of human xenograft tumors which harbored various mutations. These findings suggest that MEDI-565 represents a potential treatment option for patients with CEA positive tumors of diverse origin, including those with individual or combinations of somatic mutations that may be less responsive to chemotherapy and other targeted agents.

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“…In 1977, Leon et al (12) reported increased levels of serum DNA in cancer patients compared with healthy controls. This was followed by other studies showing elevated levels of circulating serum or plasma DNA in patients with malignant tumors compared with benign controls (13)(14)(15)(16)(17)(18)(19). Sozzi et al (17) examined plasma fcDNA levels as a marker for lung cancer and found that the median fcDNA levels in plasma were 8 times greater in cancer than that in control samples (area under the curve, 0.94).…”

Section: Introductionmentioning

confidence: 95%

Serum Free Circulating DNA Is a Useful Biomarker to Distinguish Benign versus Malignant Prostate Disease

Gordián¹,

Ramachandran²,

Reis³

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Free circulating DNA (fcDNA) has been shown to be elevated in serum of prostate cancer patients compared with benign controls. However, studies evaluating the role of fcDNA as a biomarker in a "representative" patient group who have undergone prostate cancer screening are lacking. Our study examined the use of serum fcDNA levels as a biomarker of prostate cancer in such a setting.Methods: The study included 252 men, with prostate-specific antigen (PSA) levels >4 ng/mL and/or abnormal digital rectal exam. fcDNA levels in serum before prostate biopsy were quantitated by real-time PCR amplification of the glutathione S-transferase, pi, gene.Results: Patients with PSA ≤ 10 ng/mL with fcDNA > 180 ng/mL were at increased risk for prostate cancer compared with those with fcDNA ≤180 ng/mL (odds ratio, 4.27; 95% confidence interval, 2.05-8.88; P < 0.001; area under the curve, 0.742). The multivariate model including age, race, PSA, fcDNA, and interaction between fcDNA and PSA yielded a high negative predictive value of 93.1% and increased specificity of 33.1% compared with negative predictive value of 73.3% and specificity of 6.7% in the model excluding fcDNA.Conclusions: Our results indicate that fcDNA may improve the specificity of prostate cancer screening. Impact: Our study shows that adding fcDNA to prostate cancer screening can reduce the number of unnecessary prostate biopsies. Cancer Epidemiol Biomarkers Prev; 19(8); 1984-91. ©2010 AACR.

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Free DNA and Carcinoembryonic Antigen Serum Levels: An Important Combination for Diagnosis of Colorectal Cancer

Cited by 112 publications

References 23 publications

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas

Serum Free Circulating DNA Is a Useful Biomarker to Distinguish Benign versus Malignant Prostate Disease

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