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https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#1
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 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28400627/molecular-subtypes-in-cancers-of-the-gastrointestinal-tract
#2
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...
April 12, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28373362/pancreatic-cancer-genomes-implications-for-clinical-management-and-therapeutic-development
#3
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
#4
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H M W 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
#5
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 employed in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several issues 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...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28240774/early-detection-of-pancreatic-cancer-where-are-we-now-and-where-are-we-going
#6
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)...
February 27, 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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27845911/deciphering-the-link-between-pi3k-and-pak-an-opportunity-to-target-key-pathways-in-pancreatic-cancer
#11
REVIEW
Kiruthikah Thillai, Hoyin Lam, Debashis Sarker, Claire M Wells
The development of personalised therapies has ushered in a new and exciting era of cancer treatment for a variety of solid malignancies. Yet pancreatic ductal adenocarcinoma (PDAC) has failed to benefit from this paradigm shift, remaining notoriously refractory to targeted therapies. Chemotherapy is the cornerstone of management but can offer only modest survival benefits of a few months with 5-year survival rates rarely exceeding 3%. Despite these disappointing statistics, significant strides have been made towards understanding the complex biology of pancreatic cancer, with deep genomic sequencing identifying novel genetic aberrations and key signalling pathways...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27708512/genetic-factors-affecting-patient-responses-to-pancreatic-cancer-treatment
#12
REVIEW
George Fotopoulos, Konstantinos Syrigos, Muhammad Wasif Saif
Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy...
October 2016: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/27688185/k-ras-and-its-inhibitors-towards-personalized-cancer-treatment-pharmacological-and-structural-perspectives
#13
REVIEW
Vivek Asati, Debarshi Kar Mahapatra, Sanjay Kumar Bharti
The discovery of genetic, genomic and clinical biomarkers have revolutionized the treatment option in the form of personalized medicine which allows to accurately predict a person's susceptibility/progression of disease, the patient's response to therapy, and maximize the therapeutic outcome in terms of low/no toxicity for a particular patient. Recently, the U.S. Food and Drug Administration has realized the contribution of pharmacogenomics in better healthcare and advocated the consideration of pharmacogenomic principles in making safer and more effective drug...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27630273/paradoxical-role-of-hmgb1-in-pancreatic-cancer-tumor-suppressor-or-tumor-promoter
#14
REVIEW
María José García Cebrián, Monika Bauden, Roland Andersson, Stefan Holdenrieder, Daniel Ansari
Pancreatic cancer has a dismal prognosis and there is an increasing and unmet need to identify better diagnostic and therapeutic targets in order to ameliorate the course of the disease. HMGB1, a nuclear DNA-binding protein that acts as a transcription factor, is currently in the limelight. HMGB1 exhibits a dual role in pancreatic cancer; when intracellular, it acts as an anti-tumor protein stabilizing the genome, whereas extracellular HMGB1 behaves as a pro-tumor protein with cytokine, chemokine and growth factor functions...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27621332/current-and-evolving-therapies-for-metastatic-pancreatic-cancer-are-we-stuck-with-cytotoxic-chemotherapy
#15
REVIEW
Gauri R Varadhachary, Robert A Wolff
At present, front-line therapy for metastatic pancreatic ductal adenocarcinoma is combination chemotherapy, most commonly FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) or gemcitabine and nanoparticle albumin-bound paclitaxel. Despite a better understanding of the genomic landscape and the importance of the tumor microenvironment, we have not made a seismic shift in the overall survival for this disease. Given our growing understanding of the biology of pancreatic ductal adenocarcinoma, the question remains whether novel, noncytotoxic agents will augment or even replace conventional chemotherapy...
September 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/27498575/advances-in-understanding-the-molecular-mechanism-of-pancreatic-cancer-metastasis
#16
REVIEW
Yong-Xing Du, Zi-Wen Liu, Lei You, Wen-Ming Wu, Yu-Pei Zhao
BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015...
August 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27444064/pancreatic-cancer-biology-and-genetics-from-an-evolutionary-perspective
#17
Alvin Makohon-Moore, Christine A Iacobuzio-Donahue
Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease...
September 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27345450/-new-molecular-classification-of-colorectal-cancer-pancreatic-cancer-and-stomach-cancer-towards-%C3%A3-la-carte-treatment
#18
REVIEW
Chantal Dreyer, Pauline Afchain, Isabelle Trouilloud, Thierry André
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion)...
July 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27297136/inflammation-as-a-driver-and-vulnerability-of-kras-mediated-oncogenesis
#19
REVIEW
Shunsuke Kitajima, Rohit Thummalapalli, David A Barbie
While important strides have been made in cancer therapy by targeting certain oncogenes, KRAS, the most common among them, remains refractory to this approach. In recent years, a deeper understanding of the critical importance of inflammation in promoting KRAS-driven oncogenesis has emerged, and applies across the different contexts of lung, pancreatic, and colorectal tumorigenesis. Here we review why these tissue types are particularly prone to developing KRAS mutations, and how inflammation conspires with KRAS signaling to fuel carcinogenesis...
October 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27170400/molecular-pathogenesis-and-current-therapy-in-intrahepatic-cholangiocarcinoma
#20
REVIEW
Dan Høgdall, Colm J O'Rourke, Andrzej Taranta, Douglas V N P Oliveira, Jesper B Andersen
Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current clinical strategies and patient outcome...
2016: Digestive Diseases
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