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Review genomic pancreatic cancer

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https://www.readbyqxmd.com/read/28689205/genomics-in-primary-and-secondary-prevention-of-pancreatic-cancer
#1
Núria Malats, Esther Molina-Montes, Carlo La Vecchia
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...
July 8, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28682795/genetics-of-pancreatic-cyst-cancer-progression-standing-on-the-shoulders-of-giants
#2
Bhuwan Giri, Vrishketan Sethi, Vikas Dudeja, Sulagna Banerjee, Alan Livingstone, Ashok Saluja
PURPOSE OF REVIEW: Pancreatic cancer, despite years of study and some progress, presents with a grim prognosis in almost all cases. In the current review, we have discussed recent studies that have attempted to decipher the genetic makeup of pancreatic ductal adenocarcinoma and preneoplastic pancreatic cystic neoplasms. RECENT FINDINGS: With the advent of high throughput sequencing, the genetic code of pancreatic cancer is beginning to unravel and this new-found information heralds an era of precision cancer care where treatment will be guided by the genetic code of the neoplasm...
July 5, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28638788/histone-deacetylases-microrna-and-leptin-crosstalk-in-pancreatic-cancer
#3
REVIEW
Cynthia I Tchio Mantho, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Because pancreatic cancer (PC) historically has had poor prognosis and five year survival rates, it has been intensely investigated. Analysis of PC incidence and biology has shown a link between different risk factors such as smoking, alcoholism, and obesity and disease progression. Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation, and actions of microRNA inducing oncogenic or tumor suppressor effects. Studies have identified markers whose dysregulation seem to play important roles in PC progression...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#4
REVIEW
Marie Rouanet, Marine Lebrin, Fabian Gross, Barbara Bournet, Pierre Cordelier, Louis Buscail
A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes)...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28587243/genomic-variations-in-pancreatic-cancer-and-potential-opportunities-for-development-of-new-approaches-for-diagnosis-and-treatment
#5
REVIEW
Shuangshuang Lu, Tasqeen Ahmed, Pan Du, Yaohe Wang
Human pancreatic cancer has a very poor prognosis with an overall five-year survival rate of less than 5% and an average median survival time of six months. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Although our understanding of the molecular events underlying multi-step carcinogenesis in pancreatic cancer has steadily increased, translation into more effective therapeutic approaches has been inefficient in recent decades. Therefore, it is imperative that novel and targeted approaches are designed to facilitate the early detection and treatment of pancreatic cancer...
June 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537880/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#6
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...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536860/line-1-methylation-level-and-prognosis-in-pancreas-cancer-pyrosequencing-technology-and-literature-review
#7
Kensuke Yamamura, Keisuke Kosumi, Yoshifumi Baba, Kazuto Harada, Feng Gao, Xiaobo Zhang, Lei Zhou, Yuki Kitano, Kota Arima, Takayoshi Kaida, Hideaki Takeyama, Takaaki Higashi, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Xiaodong Tan, Hideo Baba
PURPOSE: Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear. METHODS: We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level...
May 23, 2017: Surgery Today
https://www.readbyqxmd.com/read/28504904/application-of-panel-based-tests-for-inherited-risk-of-cancer
#8
Payal D Shah, Katherine L Nathanson
Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. When evaluating the inherited risk of breast and ovarian cancers, panel-based tests provide incremental benefit compared with BRCA1/2 genetic testing. For inherited risk of other cancers, such as colon cancer and pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based testing are higher; in fact, simultaneous evaluation of multiple genes has been the historical standard for these diseases...
May 15, 2017: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/28460572/next-generation-sequencing-of-pancreatic-ductal-adenocarcinoma-right-or-wrong
#9
Ashton A Connor, Steven Gallinger
Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all epithelial malignancies and a paradoxically rising incidence rate. Clinical translation of next generation sequencing (NGS) of tumour and germline samples may ameliorate outcomes by identifying prognostic and predictive genomic and transcriptomic features in appreciable fractions of patients, facilitating enrolment in biomarker-matched trials. Areas covered: The literature on precision oncology is reviewed. It is found that outcomes may be improved across various malignancies, and it is suggested that current issues of adequate tissue acquisition, turnaround times, analytic expertise and clinical trial accessibility may lessen as experience accrues...
May 10, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28452926/kras-tp53-cdkn2a-smad4-brca1-and-brca2-mutations-in-pancreatic-cancer
#10
REVIEW
Jonas Cicenas, Kotryna Kvederaviciute, Ingrida Meskinyte, Edita Meskinyte-Kausiliene, Aiste Skeberdyte, Jonas Cicenas
Pancreatic cancer is a disease that has a very high fatality rate and one of the highest mortality ratios among all major cancers, remaining the fourth leading cause of cancer-related deaths in developed countries. The major treatment of pancreatic cancer is surgery; however, only 15-20% of patients are candidates for it at the diagnosis of disease. On the other hand, survival in patients, who undergo surgery, is less than 30%. In most cancers, genome stability is disturbed and pancreatic cancer is not the exception...
April 28, 2017: Cancers
https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#11
REVIEW
E Giovannetti, C L van der Borden, A E Frampton, A Ali, O Firuzi, G J Peters
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis...
April 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28400627/molecular-subtypes-in-cancers-of-the-gastrointestinal-tract
#12
REVIEW
Maarten F Bijlsma, Anguraj Sadanandam, Patrick Tan, Louis Vermeulen
Malignancies of the gastrointestinal tract are among the most common human cancers. The distinct tissues of origin give rise to a diverse set of diseases, such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each associating with specific clinical features. Genomic and transcriptomic analyses have further defined the heterogeneity that occurs within these cancers by identifying so-called molecular subtypes. These subtypes are characterized by specific genetic aberrations and expression signatures that suggest important biological differences...
June 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28373362/pancreatic-cancer-genomes-implications-for-clinical-management-and-therapeutic-development
#13
EDITORIAL
Stephan B Dreyer, David K Chang, Peter Bailey, Andrew V Biankin
Pancreatic cancer has become the third leading cause of cancer-related death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet only 20% of patients will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers and beyond that, a low prevalence for targetable mutations...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28366542/key-biological-processes-driving-metastatic-spread-of-pancreatic-cancer-as-identified-by-multi-omics-studies
#14
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H W M van Laarhoven, E Giovannetti, C R Jimenez
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood...
March 30, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28266780/recent-advances-in-genetic-modification-of-adenovirus-vectors-for-cancer-treatment
#15
REVIEW
Yuki Yamamoto, Masaki Nagasato, Teruhiko Yoshida, Kazunori Aoki
Adenoviruses are widely used to deliver genes to a variety of cell types and have been used in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several concerns must be addressed for the clinical use of adenovirus vectors. Selective delivery of a therapeutic gene by adenovirus vectors to target cancer is precluded by the widespread distribution of the primary cellular receptors. The systemic administration of adenoviruses results in hepatic tropism independent of the primary receptors...
May 2017: Cancer Science
https://www.readbyqxmd.com/read/28240774/early-detection-of-pancreatic-cancer-where-are-we-now-and-where-are-we-going
#16
REVIEW
Bin Zhou, Jian-Wei Xu, Yu-Gang Cheng, Jing-Yue Gao, San-Yuan Hu, Lei Wang, Han-Xiang Zhan
Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva)...
July 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28176634/targeting-the-akt-pi3k-signaling-pathway-as-a-potential-therapeutic-strategy-for-the-treatment-of-pancreatic-cancer
#17
Safieh Ebrahimi, Mina Hosseini, Soodabeh Shahidsales, Mina Maftouh, Gordon A Ferns, Majid Ghayour-Mobarhan, Seyed Mahdi Hassanian, Amir Avan
The phosphoinositide 3 kinase AKT mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway is an important signaling pathway in pancreatic cancer (PC). It is frequently activated in PC and is associated with worse outcome. Aberrant activation of this pathway is involved in cell metabolism and survival, cell cycle progression, regulation of apoptosis, protein synthesis, and genomic instability. Several agents have been developed to target Akt/PI3K pathways, including PI3K inhibitors, (e.g. LY294002, Wortmannin), PI3K/mTOR inhibitors (e...
February 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#18
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#19
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#20
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
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