scholarly journals Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7651
Author(s):  
Miles W. Grunvald ◽  
Richard A. Jacobson ◽  
Timothy M. Kuzel ◽  
Sam G. Pappas ◽  
Ashiq Masood

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.

2016 ◽  
Vol 23 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Daniel Pietrasz ◽  
Nicolas Pécuchet ◽  
Fanny Garlan ◽  
Audrey Didelot ◽  
Olivier Dubreuil ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 288-288 ◽  
Author(s):  
Julia S. Johansen ◽  
Cecile Rose T. Vibat ◽  
Dan Calatayud ◽  
Benny Vittrup Jensen ◽  
Jane Preuss Hasselby ◽  
...  

288 Background: Non-resectable pancreatic cancer patients have a wide range of median time for overall survival (OS). Currently there is a lack of diagnostic tools to predict patient outcome at diagnosis. KRAS mutations are present in the vast majority of pancreatic tumors. The study objective was to determine if quantitative baseline and longitudinal monitoring of KRAS mutations from plasma circulating tumor DNA (ctDNA) could be used to stratify patients for predicting outcome. Methods: Plasma was prospectively collected from the Danish BIOPAC study for non-resectable pancreatic cancer patients undergoing treatment with gemcitabine or FOLFIRINOX. Feasibility of monitoring ctDNA KRAS mutations was assessed in 10 patients with long OS (median 493 days; range 360-1031) and 10 patients with short OS (median 66 days; range 21-136). KRAS G12A/C/D/R/S/V, and G13D mutations were PCR enriched, sequenced by massively parallel deep sequencing, quantitated and standardized by reporting number of copies detected per 105 genome equivalents (GE). Results: In a pilot study of 20 patients, all 18 patients with evaluable DNA had detectable KRAS mutations. Of 18 patients, 12 had baseline plus longitudinal time points (7 short, 5 long OS). Mutant KRAS copies were higher for short OS (median=994; range 0-34305 copies/105 GE) vs. with long OS (median 196; range, 34-278 copies/105 GE). Longitudinally, KRAS mutation levels remained mostly low with long OS (last time point median 204; range 8-873 copies/105 GE) vs. short OS where levels increased or remained high (median 2363; range 71-47919 copies/105 GE). Identical KRAS mutations were consistently detected for a given patient with short OS. However, long OS patients had variable KRAS mutations in longitudinal analysis. Conclusions: High levels of ctDNA KRAS mutations at diagnosis and post-treatment elevation of KRAS mutations were more associated with short OS. Different levels of KRAS mutation at diagnosis may predict patient outcome and could reflect distinct underlying tumor biology. Expansion of this prospective-retrospective biomarker cohort will be reported.


2020 ◽  
Author(s):  
Carmen Rubio Alarcón ◽  
Dave E. van der Kruijssen ◽  
Lana Meiqari ◽  
Linda J. Bosch ◽  
John K. Simmons ◽  
...  

2020 ◽  
Vol 31 ◽  
pp. S180-S181
Author(s):  
A. Popova ◽  
M. Fedyanin ◽  
I. Pokataev ◽  
D. Shamovskaya ◽  
N. Kudashkin ◽  
...  

2020 ◽  
Vol 14 (8) ◽  
pp. 1670-1679 ◽  
Author(s):  
Tenna V. Henriksen ◽  
Thomas Reinert ◽  
Emil Christensen ◽  
Himanshu Sethi ◽  
Karin Birkenkamp‐Demtröder ◽  
...  

2019 ◽  
Vol 63 (6) ◽  
pp. 456-465 ◽  
Author(s):  
Joana Fernandes Marques ◽  
Joana Pereira Reis ◽  
Gabriela Fernandes ◽  
Venceslau Hespanhol ◽  
José Carlos Machado ◽  
...  

Liquid biopsy was introduced to the oncology field with the promise of revolutionizing the management of cancer patients, minimizing the exposure to invasive procedures such as tissue biopsy, and providing reliable information regarding therapy response and detection of disease relapse. Despite the significant increase in the number of published studies on circulating tumor DNA (ctDNA) in the past years, the emphasis of most studies is on the development of new technologies or on the clinical utility of ctDNA. This leaves a clear gap of knowledge concerning the biology of ctDNA, such as the fundamental mechanisms through which DNA from tumor cells is released into the circulation. Moreover, considering that ctDNA analysis is now currently being applied in clinical practice, the need for rigorous quality control is arising, and with it the necessity to standardize procedures, from sample collection to data analysis. This review focuses on the main aspects of ctDNA, including approaches currently available to evaluate tumor genetics, as well as the points that still require improvement in order to make liquid biopsy a key player in precision medicine.


2019 ◽  
Vol 156 (6) ◽  
pp. S-760
Author(s):  
Kazuyoshi Ohkawa ◽  
Ryoji Takada ◽  
Kenji Ikezawa ◽  
Nobuyasu Fukutake ◽  
Abe Yutaro ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guanhua Zhu ◽  
Yu A. Guo ◽  
Danliang Ho ◽  
Polly Poon ◽  
Zhong Wee Poh ◽  
...  

AbstractProfiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients. Using compact targeted sequencing (<25 kb) of predictive regions, we demonstrate how the approach could enable quantitative low-cost tracking of ctDNA dynamics and disease progression.


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