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Pancreatic Neoplasms: HELP
Articles by Nancy A. Jenkins
Based on 4 articles published since 2009
(Why 4 articles?)
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Between 2009 and 2019, Nancy A. Jenkins wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review KRAS-related proteins in pancreatic cancer. 2016

Mann, Karen M / Ying, Haoqiang / Juan, Joseph / Jenkins, Nancy A / Copeland, Neal G. ·Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: kmmann@houstonmethodist.org. · Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA. · Molecular Oncology Department, Genentech, Inc., South San Francisco, CA 94080, USA. · Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA. ·Pharmacol Ther · Pubmed #27595930.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with a high mortality rate. Genetic and biochemical studies have shown that RAS signaling mediated by KRAS plays a pivotal role in disease initiation, progression and drug resistance. RAS signaling affects several cellular processes in PDAC, including cellular proliferation, migration, cellular metabolism and autophagy. 90% of pancreatic cancer patients harbor somatic oncogenic point mutations in KRAS, which lead to constitutive activation of the molecule. Pancreatic cancers lacking KRAS mutations show activation of RAS via upstream signaling through receptor mediated tyrosine kinases, like EGFR, and in a small fraction of patients, oncogenic activation of the downstream B-RAF molecule is detected. RAS-stimulated signaling of RAF/MEK/ERK, PI3K/AKT/mTOR and RalA/B is active in human pancreatic cancers, cancer cell lines and mouse models of PDAC, although activation levels of each signaling arm appear to be variable across different tumors and perhaps within different subclones of single tumors. Recently, several targeted therapies directed towards MEK, ERK, PI3K and mTOR have been assayed in pancreatic cancer cell lines and in mouse models of the disease with promising results for their ability to impede cellular growth or delay tumor formation, and several inhibitors are currently in clinical trials. However, therapy-induced cross activation of RAS effector molecules has elucidated the complexities of targeting RAS signaling. Combinatorial therapies are now being explored as an approach to overcome RAS-induced therapeutic resistance in pancreatic cancer.

2 Review Sleeping Beauty mutagenesis: exploiting forward genetic screens for cancer gene discovery. 2014

Mann, Michael B / Jenkins, Nancy A / Copeland, Neal G / Mann, Karen M. ·Cancer Research Program, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, United States. · Cancer Research Program, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, United States. Electronic address: kmmann@HoustonMethodist.org. ·Curr Opin Genet Dev · Pubmed #24657532.

ABSTRACT: Sleeping Beauty (SB) is a powerful insertional mutagen used in somatic forward genetic screens to identify novel candidate cancer genes. In the past two years, SB has become widely adopted to model human pancreatic, hepatocellular, colorectal and neurological cancers to identify loci that participate in tumor initiation, progression and metastasis. Oncogenomic approaches have directly linked hundreds of genes identified by SB with human cancers, many with prognostic implications. These SB candidate cancer genes are aiding to prioritize punitive human cancer genes for follow-up studies and as possible biomarkers or therapeutic targets. This review highlights recent advances in SB cancer gene discovery, approaches to validate candidate cancer genes, and efforts to integrate SB data across all tumor types to prioritize drug development and tumor specificity.

3 Article Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. 2012

Biankin, Andrew V / Waddell, Nicola / Kassahn, Karin S / Gingras, Marie-Claude / Muthuswamy, Lakshmi B / Johns, Amber L / Miller, David K / Wilson, Peter J / Patch, Ann-Marie / Wu, Jianmin / Chang, David K / Cowley, Mark J / Gardiner, Brooke B / Song, Sarah / Harliwong, Ivon / Idrisoglu, Senel / Nourse, Craig / Nourbakhsh, Ehsan / Manning, Suzanne / Wani, Shivangi / Gongora, Milena / Pajic, Marina / Scarlett, Christopher J / Gill, Anthony J / Pinho, Andreia V / Rooman, Ilse / Anderson, Matthew / Holmes, Oliver / Leonard, Conrad / Taylor, Darrin / Wood, Scott / Xu, Qinying / Nones, Katia / Fink, J Lynn / Christ, Angelika / Bruxner, Tim / Cloonan, Nicole / Kolle, Gabriel / Newell, Felicity / Pinese, Mark / Mead, R Scott / Humphris, Jeremy L / Kaplan, Warren / Jones, Marc D / Colvin, Emily K / Nagrial, Adnan M / Humphrey, Emily S / Chou, Angela / Chin, Venessa T / Chantrill, Lorraine A / Mawson, Amanda / Samra, Jaswinder S / Kench, James G / Lovell, Jessica A / Daly, Roger J / Merrett, Neil D / Toon, Christopher / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Anonymous1421514 / Kakkar, Nipun / Zhao, Fengmei / Wu, Yuan Qing / Wang, Min / Muzny, Donna M / Fisher, William E / Brunicardi, F Charles / Hodges, Sally E / Reid, Jeffrey G / Drummond, Jennifer / Chang, Kyle / Han, Yi / Lewis, Lora R / Dinh, Huyen / Buhay, Christian J / Beck, Timothy / Timms, Lee / Sam, Michelle / Begley, Kimberly / Brown, Andrew / Pai, Deepa / Panchal, Ami / Buchner, Nicholas / De Borja, Richard / Denroche, Robert E / Yung, Christina K / Serra, Stefano / Onetto, Nicole / Mukhopadhyay, Debabrata / Tsao, Ming-Sound / Shaw, Patricia A / Petersen, Gloria M / Gallinger, Steven / Hruban, Ralph H / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Schulick, Richard D / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Capelli, Paola / Corbo, Vincenzo / Scardoni, Maria / Tortora, Giampaolo / Tempero, Margaret A / Mann, Karen M / Jenkins, Nancy A / Perez-Mancera, Pedro A / Adams, David J / Largaespada, David A / Wessels, Lodewyk F A / Rust, Alistair G / Stein, Lincoln D / Tuveson, David A / Copeland, Neal G / Musgrove, Elizabeth A / Scarpa, Aldo / Eshleman, James R / Hudson, Thomas J / Sutherland, Robert L / Wheeler, David A / Pearson, John V / McPherson, John D / Gibbs, Richard A / Grimmond, Sean M. ·The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia. ·Nature · Pubmed #23103869.

ABSTRACT: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

4 Article Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma. 2012

Mann, Karen M / Ward, Jerrold M / Yew, Christopher Chin Kuan / Kovochich, Anne / Dawson, David W / Black, Michael A / Brett, Benjamin T / Sheetz, Todd E / Dupuy, Adam J / Anonymous6720720 / Chang, David K / Biankin, Andrew V / Waddell, Nicola / Kassahn, Karin S / Grimmond, Sean M / Rust, Alistair G / Adams, David J / Jenkins, Nancy A / Copeland, Neal G. ·Division of Genetics and Genomics, Institute of Molecular and Cell Biology, Singapore 138673. ·Proc Natl Acad Sci U S A · Pubmed #22421440.

ABSTRACT: Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by SB in these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer. We identified point mutations in human pancreatic patient samples for another 11 CCGs, including Acvr2a and Map2k4. Importantly, 10% of the CCGs are involved in chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1, Fbxo11, and Vgll4, are also significantly associated with poor patient survival. SB mutagenesis provides a rich resource of mutations in potential cancer drivers for cross-comparative analyses with ongoing sequencing efforts in human pancreatic adenocarcinoma.