Pancreatic cancer

Kleeff, Jörg; Korc, Murray; Apte, Minoti V.; Vecchia, Carlo La; Johnson, C. D.; Biankin, Andrew V.; Neale, Rachel E.; Tempero, Margaret A.; Tuveson, David A.; Hruban, Ralph H.; Neoptolemos, John P.

doi:10.1038/nrdp.2016.22

Cited by 1,381 publications

(1,160 citation statements)

References 269 publications

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“…Despite intense research efforts over the last decade, pancreatic ductal adenocarcinoma (PDA) is still considered one of the most aggressive and lethal solid tumours 1. Survival statistics have hardly changed, with most patients struggling to survive the first year after diagnosis, and a 5-year survival rate at 7% 1.…”

Section: Introductionmentioning

confidence: 99%

“…Survival statistics have hardly changed, with most patients struggling to survive the first year after diagnosis, and a 5-year survival rate at 7% 1. Early diagnosis is still an unresolved problem as the vast majority (>80%) of patients are diagnosed with advanced or metastatic disease, and even for early stage tumours, relapse rate is high.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

Neeße

Bauer

Öhlund

et al. 2018

Gut

257

206

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Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

Neeße

Bauer

Öhlund

et al. 2018

Gut

257

206

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“…The causes and development of the deadly disease, pancreatic ductal adenocarcinoma (PDAC), are barely understood 1. Pancreatitis is an established significant risk factor for PDAC 2.…”

Section: Introductionmentioning

confidence: 99%

Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy

Kong

Bruns

Behler

et al. 2016

Gut

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Objective The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. Design We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. Results We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. Conclusions These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis.

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“…Furthermore, for the majority of the identified risk factors, the associations are generally modest, making it difficult to identify a high-risk group that would benefit from screening. PC is one of the deadliest cancers worldwide with a 5-year survival rate of up to 7% [10] . Furthermore, this is the single common cancer for which there has been no improvement in its fatal prognosis over the last decades, despite the efforts in tertiary prevention since the tumor is overall resistant to treatment.…”

Section: Tumor-genomics Markersmentioning

confidence: 99%

Genomics in Primary and Secondary Prevention of Pancreatic Cancer

Malats

Molina‐Montes²,

Vecchia³

2017

Public Health Genomics

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Background: Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon. Aims/Objectives: To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field. Methods: A review of the literature was performed to identify germline and tumor DNA and RNA markers that showed potential usefulness in defining the high-risk population, diagnosing the disease early, and identifying new carcinogens associated with PC. Results: Only high-penetrance inherited mutations are used, at present, to define the high-risk PC population. Although there are some promising genomics markers to be used as early detection tests, none has been validated adequately to be integrated into the clinics routine. Conclusions: Despite of important efforts made in the recent time, little progress has been made to better characterise high-risk PC populations and to identify genomics-based markers for its early diagnosis. PC rates continue to rise, and this disease is becoming a real public health problem in the Westernised world. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed to implement cost-efficient primary and secondary prevention interventions in PC.

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Pancreatic cancer

Cited by 1,381 publications

References 269 publications

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy

Genomics in Primary and Secondary Prevention of Pancreatic Cancer

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