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https://www.readbyqxmd.com/read/29537309/pancreatic-cancer-subtypes-a-roadmap-for-precision-medicine
#1
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as a disease, accumulated evidences point to the clinical heterogeneity of this disease, which translate into disparity in outcomes among the patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last 10 years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 22, 2018: Annals of Medicine
https://www.readbyqxmd.com/read/29499330/molecular-classification-as-prognostic-factor-and-guide-for-treatment-decision-of-pancreatic-cancer
#2
REVIEW
David J Birnbaum, François Bertucci, Pascal Finetti, Daniel Birnbaum, Emilie Mamessier
Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for oancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter and intra tumor genetic heterogeneity. A molecular classification should help reduce heterogeneity among patients, with the consequences of better predicting evolution and better orienting the treatment. This review summarizes the information that should be retained in clinical practice from all the molecular analyses. PDAC can be classified based on mutational subtypes and gene alterations...
February 27, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29491046/centrosomal-abnormalities-in-pancreatic-cancer-molecular-mechanisms-and-clinical-implications
#3
REVIEW
Daniel Ansari, Carolina Del Pino Bellido, Monika Bauden, Roland Andersson
The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes...
March 2018: Anticancer Research
https://www.readbyqxmd.com/read/29483830/the-role-of-tgf-%C3%AE-smad4-signaling-in-cancer
#4
REVIEW
Ming Zhao, Lopa Mishra, Chu-Xia Deng
Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29463004/advanced-eus-guided-tissue-acquisition-methods-for-pancreatic-cancer
#5
REVIEW
Pujan Kandel, Michael B Wallace
Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer...
February 17, 2018: Cancers
https://www.readbyqxmd.com/read/29367431/evaluating-mismatch-repair-deficiency-in-pancreatic-adenocarcinoma-challenges-and-recommendations
#6
Zishuo I Hu, Jinru Shia, Zsofia K Stadler, Anna M Varghese, Marinela Capanu, Erin Salo-Mullen, Maeve A Lowery, Luis A Diaz, Diana Mandelker, Kenneth H Yu, Alice Zervoudakis, David P Kelsen, Christine A Iacobuzio-Donahue, David S Klimstra, Leonard Saltz, Ibrahim H Sahin, Eileen M O'Reilly
PURPOSE: Immune checkpoint inhibition has been shown to generate profound and durable responses in MMR-D solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D PDAC and assess the utility of NGS in providing additional prognostic and predictive information for MMR-D PDAC. EXPERIMENTAL DESIGN: Archival and prospectively acquired samples and matched normal DNA from N= 833 PDAC cases were analyzed using a hybridization capture based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341- 468 cancer-associated genes...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29258858/emerging-biomarkers-for-immunomodulatory-cancer-treatment-of-upper-gastrointestinal-pancreatic-and-hepatic-cancers
#7
REVIEW
Belinda Lee, Ryan Hutchinson, Hui-Li Wong, Jeanne Tie, Tracy Putoczki, Ben Tran, Peter Gibbs, Michael Christie
Carcinomas of the oesophagus, stomach, pancreas and liver are common and account for a disproportionately high number of cancer deaths. There is a need for new treatment options for patients with advanced disease. Immunomodulatory treatments including immune checkpoint blockade offer a promising new approach, with efficacy shown in other solid tumour types. However, only a small proportion of patients with carcinomas of the oesophagus, stomach, pancreas and liver have responded to single agent checkpoint inhibitors, and there is a need for markers that are predictive of response to guide treatment of individual patients...
December 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29177584/sirtuin-6-a-possible-therapeutic-target-for-type-2-diabetes
#8
REVIEW
Eun Ju Bae
Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family, localizes in the nucleus and primarily regulates chromatin signaling and genomic integrity. Recent studies established the critical role of SIRT6 in the pathophysiology of metabolic disease, as well as its roles in longevity and cancer. These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes...
December 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29168653/utilizing-biomarkers-in-colorectal-cancer-an-interview-with-ajay-goel
#9
Ajay Goel
Ajay Goel speaks to Rachel Jenkins, Commissioning Editor. Ajay Goel, PhD, is a Professor and Director, Center for Gastrointestinal Research, and Director, Center for Translational Genomics and Oncology, at the Baylor Scott & White Research Institute, Baylor University Medical Center in Dallas, Texas. Dr Goel has spent more than 20 years researching cancer and has been the lead author or contributor to over 240 scientific articles published in peer-reviewed international journals and several book chapters...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29118556/long-non-coding-rna-in-pancreatic-adenocarcinoma-and-pancreatic-neuroendocrine-tumors
#10
REVIEW
Dimitrios Moschovis, Maria Gazouli, Maria Tzouvala, Antonios Vezakis, George Karamanolis
Interest in non-coding regions of DNA has been increasing since the mapping of the human genome revealed that human DNA contains far fewer genes encoding proteins than previously expected. However, analysis of the derivatives of DNA transcription (transcriptomics) revealed that the majority of the genetic material is transcribed into non-coding RNA (ncRNA), indicating that these molecules probably provide the functional diversity and complexity of the physiology of the human body that cannot be attributed to the proteins...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/29063873/future-role-of-endoscopic-ultrasound-in-personalized-management-of-pancreatic-cancer
#11
REVIEW
Marie Ooi, An Phan, Nam Q Nguyen
Pancreatic ductal adenocarcinoma (PDAC) is aggressive and lethal with the majority of cases presenting with advanced unresectable disease due to delayed diagnosis. Despite improvement in surgery, chemotherapies, and intensive care medicine, the outcome of PDAC remains poor, which may relate to the tumor biology. Recent data suggest that PDAC is a "systemic cancer" with complex molecular or genomics derangement with marked heterogeneity. The ability to characterize the PDAC better by detailed evaluation of tissue biomarkers or genomics allows for improved prediction of prognosis and stratification of treatment, a concept known as "personalized cancer therapy...
September 2017: Endoscopic Ultrasound
https://www.readbyqxmd.com/read/29051346/data-driven-prioritization-and-review-of-targets-for-molecular-based-theranostic-approaches-in-pancreatic-cancer
#12
Marjory Koller, Elmire Hartmans, Derk Jan A de Groot, Xiao Juan Zhao, Gooitzen M van Dam, Wouter B Nagengast, Rudolf S N Fehrmann
Molecularly targeted therapeutic and imaging strategies directed at aberrant signaling pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient-derived normal pancreatic tissue ( n = 77) and PDA samples ( n = 103). Functional genomic messenger RNA profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of preclinical therapeutic and imaging evaluation in PDA...
December 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#13
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
November 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28915699/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#14
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914620/new-developments-in-the-molecular-mechanisms-of-pancreatic-tumorigenesis
#15
Matthäus Felsenstein, Ralph H Hruban, Laura D Wood
Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia...
March 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28869888/pancreatic-ductal-adenocarcinoma-state-of-the-art-2017-and-new-therapeutic-strategies
#16
REVIEW
Marta Chiaravalli, Michele Reni, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28858862/pancreas-cancer-precision-treatment-using-avatar-mice-from-a-bioinformatics-perspective
#17
Javier Perales-Patón, Elena Piñeiro-Yañez, Héctor Tejero, Pedro P López-Casas, Manuel Hidalgo, Gonzalo Gómez-López, Fátima Al-Shahrour
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death among solid malignancies. Unfortunately, PDAC lethality has not substantially decreased over the past 20 years. This aggressiveness is related to the genomic complexity and heterogeneity of PDAC, but also to the absence of an effective screening for the detection of early-stage tumors and a lack of efficient therapeutic options. Therefore, there is an urgent need to improve the arsenal of anti-PDAC drugs for an effective treatment of these patients...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28858227/the-role-of-palb2-in-the-dna-damage-response-and-cancer-predisposition
#18
REVIEW
Thales C Nepomuceno, Giuliana De Gregoriis, Francisco M Bastos de Oliveira, Guilherme Suarez-Kurtz, Alvaro N Monteiro, Marcelo A Carvalho
The deoxyribonucleic acid (DNA) damage response (DDR) is a major feature in the maintenance of genome integrity and in the suppression of tumorigenesis. PALB2 (Partner and Localizer of Breast Cancer 2 (BRCA2)) plays an important role in maintaining genome integrity through its role in the Fanconi anemia (FA) and homologous recombination (HR) DNA repair pathways. Since its identification as a BRCA2 interacting partner, PALB2 has emerged as a pivotal tumor suppressor protein associated to hereditary cancer susceptibility to breast and pancreatic cancers...
August 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28817982/current-challenges-in-optimizing-systemic-therapy-for-patients-with-pancreatic-cancer-expert-perspectives-from-the-australasian-gastrointestinal-trials-group-agitg-with-invited-international-faculty
#19
REVIEW
Eva Segelov, Florian Lordick, David Goldstein, Lorraine A Chantrill, Daniel Croagh, Ben Lawrence, Dirk Arnold, Ian Chau, Radka Obermannova, Timothy Jay Price
Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer...
October 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#20
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
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