Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Grunvald, Miles W; Jacobson, Richard A.; Kuzel, Timothy M.; Pappas, Sam G.; Masood, Ashiq

doi:10.3390/ijms21207651

Cited by 42 publications

(54 citation statements)

References 97 publications

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“…Combined with circulating tumor cells (CTCs) analysis, it may represent a tool to assess in real-time both tumor burden and molecular features of the disease [ 94 ]. ctDNA has been studied in patients with various cancer types, including advanced pancreatic cancer [ 95 , 96 ]. A recent meta-analysis including 19 studies further evaluates ctDNA and other liquid biopsy diagnostics, such as CTSs and blood exosomes, in PDAC detection [ 97 ].…”

Section: New Perspectivesmentioning

confidence: 99%

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Nista

Schepis

Candelli

et al. 2021

IJMS

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Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

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Section: New Perspectivesmentioning

confidence: 99%

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Nista

Schepis

Candelli

et al. 2021

IJMS

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“…In the last years, cell-free tumor DNA (ctDNA) has been acquiring a great relevance for precision medicine, since it allows us to perform a molecular characterization of the tumor in a less invasive manner and to overcome issues related to tumor heterogeneity. Although few data are available, the analysis of ctDNA could provide several advantages in clinical practice of PDAC [40] and it should be useful also for the evaluation of BRCA1/2 gene mutations, particularly when tumor tissue is not available or adequate. Moreover, interesting data have been published about the possibility to evaluate on ctDNA also BRCA1/2 reversion mutations to predict primary and acquired resistance to PARP inhibitors [41].…”

Section: Discussionmentioning

confidence: 99%

Feasibility of BRCA1/2 Testing of Formalin-Fixed and Paraffin-Embedded Pancreatic Tumor Samples: A Consecutive Clinical Series

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, with most patients diagnosed at advanced stages. First-line treatment based on a combined chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) provides limited benefits. Olaparib, a PARP inhibitor, has been approved as maintenance for PDAC patients harboring germline BRCA1/2 pathogenic mutations and previously treated with a platinum-based chemotherapy. BRCA1/2 germline testing is recommended, but also somatic mutations could predict responses to PARP inhibitors. Analysis of tumor tissues can detect both germline and somatic mutations and potential resistance alterations. Few data are available about BRCA1/2 testing on pancreatic tumor tissues, which often include limited biological material. We performed BRCA1/2 testing, by an amplicon-based Next Generation Sequencing (NGS) panel, on 37 consecutive PDAC clinical samples: 86.5% of cases were adequate for NGS analysis, with a success rate of 81.2% (median DNA input: 10 nanograms). Three BRCA2 mutations were detected (11.5%). Failed samples were all from tissue macrosections, which had higher fragmented DNA than standard sections, biopsies and fine-needle aspirations, likely due to fixation procedures. BRCA1/2 testing on pancreatic tumor tissues can also be feasible on small biopsies, but more cases must be analyzed to define its role and value in the PDAC diagnostic algorithm.

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“…The relatively low sensitivity however may have been due to the abundance of ctDNA in the circulation[ 20 ]. It has been found that the abundance of ctDNA has a positive correlation with tumour load, supported by the physiology of ctDNA mentioned above: It is released through cell death[ 22 ]. Due to this, ctDNA may not be an ideal candidate for use in early detection of PDAC but may have a role as a prognostic biomarker or a marker of response to treatment, especially in those that are CA19-9 negative.…”

Section: Biomarker Discoverymentioning

confidence: 97%

Molecular advances in pancreatic cancer: A genomic, proteomic and metabolomic approach

Rajesh

Cox

Runau

2021

WJG

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Pancreatic ductal adenocarcinoma (PDAC) represents a challenging pathology with very poor outcomes and is increasing in incidence within the general population. The majority of patients are diagnosed incidentally with insidious symptoms and hence present late in the disease process. This significantly affects patient outcomes: the only cure is surgical resection but only up to 20% of patients present with resectable disease at the time of clinical presentation. The use of “omic” technology is expanding rapidly in the field of personalised medicine - using genomic, proteomic and metabolomic approaches allows researchers and clinicians to delve deep into the core molecular processes of this difficult disease. This review gives an overview of the current findings in PDAC using these “omic” approaches and summarises useful markers in aiding clinicians treating PDAC. Future strategies incorporating these findings and potential application of these methods are presented in this review article.

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Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Cited by 42 publications

References 97 publications

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Feasibility of BRCA1/2 Testing of Formalin-Fixed and Paraffin-Embedded Pancreatic Tumor Samples: A Consecutive Clinical Series

Molecular advances in pancreatic cancer: A genomic, proteomic and metabolomic approach

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