Publications and presentations that deepen our understanding of pancreatic cancer biology.
RAS Proteins and Their Regulators in Human Disease
- Journal: Cell
- Institution(s): Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, and others
- Corresponding author(s): Frank McCormick
- Pancreatic Cancer Action Network-affiliated author: Frank McCormick, PhD, FRS: recipient, 2010 Fredman Family Foundation – Innovative Grant and member, Emeritus Scientific and Medical Advisory Board
- Major finding: RAS proteins are binary switches, cycling between ON and OFF states during signal transduction. These switches are normally tightly controlled, but in RAS-related diseases, such as cancer, RASopathies, and many psychiatric disorders, mutations in the RAS genes or their regulators render RAS proteins persistently active. The structural basis of the switch and many of the pathways that RAS controls are well known, but the precise mechanisms by which RAS proteins function are less clear. All RAS biology occurs in membranes: a precise understanding of RAS’ interaction with membranes is essential to understand RAS action and to intervene in RAS-driven diseases.
Expanding the Scope of Electrophiles Capable of Targeting K-Ras Oncogenes
- Journal: Biochemistry
- Institution(s): University of California, San Francisco, San Francisco, CA, and others
- Corresponding author(s): Gordon Mills, David Kwiatkowski or Chad Creighton
- Pancreatic Cancer Action Network-affiliated author: Kenneth Scott, PhD: recipient, 2014 Career Development Award
- Major finding: Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.
A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
- Journal: Cancer Cell
- Institution(s): Baylor College of Medicine, Houston, TX, and others
- Corresponding author(s): Kevan Shokat
- Pancreatic Cancer Action Network-affiliated author: Lynn McGregor, PhD: recipient, 2015 KRAS Fellowship
- Major finding: With a goal of targeting oncogenic K-Ras variants (e.g., G12D) by expanding the types of amino acids that can be targeted by covalent inhibitors, the authors survey a set of electrophiles for their ability to label carboxylates. Their results both demonstrate the ability of a noncatalytic cysteine to react with a diverse set of electrophiles and emphasize the importance of proper spatial arrangements between a covalent inhibitor and its intended nucleophile. They hope that these results can expand the range of electrophiles and nucleophiles of use in covalent protein modulation.
Genomic Alterations in Mucins Across Cancers
- Journal: Oncotarget
- Institution(s): University of Nebraska Medical Center, Omaha, NE
- Corresponding author(s): Pankaj Singh
- Pancreatic Cancer Action Network-affiliated author: Pankaj Singh, PhD: recipient. 2013 Career Development Award
- Major finding: The authors’ study presents a comprehensive analysis of genomic alterations in mucins and their corresponding roles in cancer progression.
Characterising Cis-regulatory Variation in the Transcriptome of Histologically Normal and Tumour-derived Pancreatic Tissues
- Journal: Gut
- Institution(s): National Cancer Institute, NIH, Bethesda, MD, and others
- Corresponding author(s): Laufey Amundadottir
- Pancreatic Cancer Action Network-affiliated author:
- Brian Wolpin, MD, MPH: co-PI, 2016 The Shirley Sadoff – Research Acceleration
- Network Grant and PI, Precision Promise Clinical Trial Consortium site
- Gloria Petersen, PhD: recipient, 2017 Early Detection Targeted Grant and member, Scientific & Medical Advisory Board
- Major finding: The authors performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. They have identified cis-eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
KIF15 Promotes Pancreatic Cancer Proliferation via the MEK-ERK Signalling Pathway
- Journal: British Journal of Cancer
- Institution(s): Renmin Hospital of Wuhan University, Wuhan, China, and others
- Corresponding author(s): Jianxin Jiang
- Major finding: This study identified KIF15 as a critical regulator that promotes pancreatic cancer proliferation, broadening our understanding of KIF15 function in tumorigenesis.
Nature and Nurture: What Determines Tumor Metabolic Phenotypes?
- Journal: Cancer Research
- Institution(s): Massachusetts Institute of Technology, Cambridge, MA, and others
- Corresponding author(s): Matthew Vander Heiden
- Major finding: These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy.