Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling

Dreyer, Stephan; Jamieson, Nigel B.; Evers, Lisa; Duthie, Fraser; Cooke, Susie; Marshall, John L.; Beraldi, Dario; Knight, Stephen R; Upstill-Goddard, Rosanna; Dickson, Euan J.; Carter, C Ross; McKay, Colin; Biankin, Andrew V.; Chang, David K.

doi:10.21037/cco.2019.04.06

Cited by 31 publications

(35 citation statements)

References 19 publications

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“…This approach, based on extra passes on EUS pancreatic biopsy and peripheral venous sampling of blood for integrated multiomic analysis, delivers molecular profiling in patients with all stages of PC with a success rate of over 80%. 98 The molecular information may guide eligibility for enrolment in a PRIMUS trial (pancreatic cancer individualised multi-arm umbrella study), investigating different biomarker-based treatment options.…”

Section: Challenges In Implementing Precision Medicine In Early-stage Pcmentioning

confidence: 99%

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Casolino

Braconi

Malleo³

et al. 2021

Annals of Oncology

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This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'allcomer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.

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Section: Challenges In Implementing Precision Medicine In Early-stage Pcmentioning

confidence: 99%

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Casolino

Braconi

Malleo³

et al. 2021

Annals of Oncology

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“…the Precision-Panc endoscopic ultrasound fine needle biopsy (FNB) training cohort (n = 54), recruited and collected during the development of the Precision-Panc(Figure 6b)43 . As in the other cohorts, this demonstrated enrichment of the squamous subtype with high replication stress (P = 0.027) and provides proof-of-principle clinical validity that the signature can be generated from FNB material and be utilized as a putative biomarker in the clinical setting.DiscussionIdentifying responsive patient subgroups is crucial to therapeutic development and improving outcomes for PC.…”

mentioning

confidence: 99%

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Dreyer

Upstill-Goddard

Paulus-Hock³

et al. 2019

Preprint

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Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting the DNA damage response (DDR) and replication stress. We show that patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum and PARP inhibitor therapy in vitro and in vivo. We generated a novel signature of replication stress with potential clinical utility in predicting response to ATR and WEE1 inhibitor treatment. Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy.

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“…A recent study by Dreyer et al[16] used genetic testing of a panel of 54 genes for 42 patients (including mostly PDAC cases, but also cases of other pancreatic lesions) using FNB samples and revealed mutations in KRAS (93%), GNAS (14%), TP53 (78%), CDKN2A (34%), and SMAD4 (32%), as well as in BRCA1(6%), ATM (12%), and BRAF (12%).…”

Section: Somatic Mutational Analyses From Eus-derived Pancreatic Cancmentioning

confidence: 99%

“…RNAseq can be used to develop a classifier profile consisting of differentially expressed genes and separate benign from malignant pancreatic tissue in 83% of cases[23]. Moreover, RNAseq was able to segregate patients into clinically relevant phenotypic subtypes (squamous and classical PDAC) in both pancreatic primary and liver metastatic lesions, showing the same subtype cluster in primary and metastatic disease[16].…”

Section: Feasibility and Clinical Utility Of Pancreatic Eus-fna/fnb Fmentioning

confidence: 99%

“…A controversial topic is whether FNB might offer advantages over FNA for DNA or RNA extraction, which is a matter of debate. As Dreyer and colleagues[16] demonstrated, DNA and RNA analyses can be performed effectively on EUS-FNB samples, but the quantity of both DNA and RNA changes based on the type of needle adopted, resulting in the highest in their cohort when adopting SharkCore 22 G (2939 ng DNA yield and 481 ng RNA yield). However, their sampling collection and conservation methods (fresh frozen or FFPE) were not matched in the same patients and the quality of RNA was not reported.…”

Section: Introductionmentioning

confidence: 99%

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New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer

Testoni

Redegalli

Petrone

et al. 2019

WJGO

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With recent advances in molecular pathology and the development of new chemotherapy regimens, the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma (PDAC) is becoming appealing for stratifying patients for prognosis and response to a defined treatment. Archival formalin-fixed, paraffin-embedded samples are a useful source of genomic deoxyribonucleic acid; nevertheless, most studies employed formalin-fixed, paraffin-embedded samples deriving from surgical specimens, which are therefore representative of <20% of PDAC patients. Indeed, the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition, stabilization, and analysis is crucial for the development of molecular markers for clinical use in order to achieve “personalized medicine”. With the development of new needles, this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures. In the present editorial, we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses, its possible pitfalls, and its use for the development of disease models such as xenografts or organoids.

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Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling

Cited by 31 publications

References 19 publications

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer

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