Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer

Lee, B; Lipton, Lara; Cohen, Joshua D.; Tie, Jeanne; Javed, Ammar A.; Li, L; Goldstein, David; Burge, Matthew; Cooray, Prasad; Nagrial, Adnan; Tebbutt, Niall C.; Thomson, Benjamin; Nikfarjam, Mehrdad; Harris, Marion; Haydon, Andrew; Lawrence, Ben; Tai, David; Simons, Koen; Lennon, Anne Marie; Wolfgang, Christopher L.; Tomasetti, Cristian; Papadopoulos, Nick; Kinzler, Kenneth W.; Vogelstein, Bert; Gibbs, Peter

doi:10.1093/annonc/mdz200

Cited by 161 publications

(144 citation statements)

References 18 publications

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“…A study of 23 patients with detectable ctDNA prior to surgical resection demonstrated that 12 converted to ctDNA-negative in the postoperative period. Of these 12, median recurrence free survival was inferior to those with undetectable preoperative ctDNA at 12.2 months compared with over 38 months in the preoperatively negative ctDNA group [ 85 ]. Early data have demonstrated that patients who have undergone neoadjuvant chemotherapy and are ctDNA negative have an 80% chance of an R0, node negative resection compared with those with who are ctDNA positive, having only a 38% chance of an R0, node negative operation [ 86 ].…”

Section: Current Clinical Utility Of Cfdnamentioning

confidence: 99%

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Grunvald

Jacobson

Kuzel

et al. 2020

IJMS

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Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians. In this publication, we aim to review cfDNA liquid biopsy in pancreatic cancer with an emphasis on current techniques, clinical utility, and areas of active investigation. We feel that researchers and clinicians alike should be familiar with this exciting modality as it gains increasing importance in the care of cancer patients.

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Section: Current Clinical Utility Of Cfdnamentioning

confidence: 99%

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Grunvald

Jacobson

Kuzel

et al. 2020

IJMS

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“…As ctDNA is believed to randomly derive from necrotic and apoptotic tumor cells across the whole tissue, it thus presumably provides a more representative genomic picture of tumor than regional tissuebased strategies. Numerous studies have shown that ctDNA profiling was able to identify and track cancerspecific mutations, which is helpful in diagnosis, prediction of prognosis, and treatment response, and guiding personalized therapeutics [11,[13][14][15]. Emerging evidence suggested the ability of genome-wide or exome-wide ctDNA sequencing to capture genetic diversity including aberrations of copy number and chromosome structure in addition to single nucleotide variants [16,17].…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide profiling of circulating tumor DNA depicts landscape of copy number alterations in pancreatic cancer with liver metastasis

Tao

Zhang

et al. 2020

Molecular Oncology

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We used whole‐genome sequencing of cell‐free DNA (cfDNA) to obtain copy number alteration (CNA) profiles from the plasma of patients with metastatic pancreatic cancer (PC). These profiles were compared with TCGA‐derived CNA profiles of primary pancreatic tumors. CNA analysis enabled the prediction of tumor burden and tumor prognosis, and assessment of therapeutic response and clonal evolution.

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“…First experiences speculated a role for ctDNA (KRAS gene mutations) in early disease diagnosis: in the study by Lennon AM et al [76] liquid biopsy specificity was high (99.5%), although at the prize of lower sensitivity (30% to 64%), meaning that in some patients tumor DNA could not be identified (probably due to overall low levels of DNA or lacking of KRAS mutations). In 2019, Gibbs P et al [77] investigated ctDNA as a surrogate marker of benefit from gemcitabine adjuvant chemotherapy in resected PDAC patients: They showed that detectable ctDNA following curative intent was associated to poor prognosis and disease relapse, despite the adjuvant chemotherapy performed; this is a precious information but requiring validation in clinical trials. Nowadays, liquid biopsy experiences to guide "in real time" PDAC therapy in advanced disease are lacking, but they are highly desirable, especially if combined to single cell genomic tools to analyze genome/transcriptome of single circulating cells.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Pancreatic Cancer Molecular Classifications: From Bulk Genomics to Single Cell Analysis

Pompella

Tirino

Pappalardo

et al. 2020

IJMS

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Pancreatic cancer represents one of the most lethal disease worldwide but still orphan of a molecularly driven therapeutic approach, although many genomic and transcriptomic classifications have been proposed over the years. Clinical heterogeneity is a hallmark of this disease, as different patients show different responses to the same therapeutic regimens. However, genomic analyses revealed quite a homogeneous disease picture, with very common mutations in four genes only (KRAS, TP53, CDKN2A, and SMAD4) and a long tail of other mutated genes, with doubtful pathogenic meaning. Even bulk transcriptomic classifications could not resolve this great heterogeneity, as many informations related to small cell populations within cancer tissue could be lost. At the same time, single cell analysis has emerged as a powerful tool to dissect intratumoral heterogeneity like never before, with possibility of generating a new disease taxonomy at unprecedented molecular resolution. In this review, we summarize the most relevant genomic, bulk and single-cell transcriptomic classifications of pancreatic cancer, and try to understand how novel technologies, like single cell analysis, could lead to novel therapeutic strategies for this highly lethal disease.

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Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer

Cited by 161 publications

References 18 publications

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Genome‐wide profiling of circulating tumor DNA depicts landscape of copy number alterations in pancreatic cancer with liver metastasis

Pancreatic Cancer Molecular Classifications: From Bulk Genomics to Single Cell Analysis

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