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KRAS Mutant Pancreatic Cancer: No Lone Path To An Effective Treatment

Daniel Zeitouni, Y. Pylayeva-Gupta, C. Der, K. L. Bryant
Published 2016 · Medicine

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Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with a dismal 7% 5-year survival rate and is projected to become the second leading cause of cancer-related deaths by 2020. KRAS is mutated in 95% of PDACs and is a well-validated driver of PDAC growth and maintenance. However, despite comprehensive efforts, an effective anti-RAS drug has yet to reach the clinic. Different paths to inhibiting RAS signaling are currently under investigation in the hope of finding a successful treatment. Recently, direct RAS binding molecules have been discovered, challenging the perception that RAS is an “undruggable” protein. Other strategies currently being pursued take an indirect approach, targeting proteins that facilitate RAS membrane association or downstream effector signaling. Unbiased genetic screens have identified synthetic lethal interactors of mutant RAS. Most recently, metabolic targets in pathways related to glycolytic signaling, glutamine utilization, autophagy, and macropinocytosis are also being explored. Harnessing the patient’s immune system to fight their cancer is an additional exciting route that is being considered. The “best” path to inhibiting KRAS has yet to be determined, with each having promise as well as potential pitfalls. We will summarize the state-of-the-art for each direction, focusing on efforts directed toward the development of therapeutics for pancreatic cancer patients with mutated KRAS.
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Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
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PDAC-ANN: an artificial neural network to predict Pancreatic Ductal Adenocarcinoma based on gene expression
Palloma Porto Almeida (2019)
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Serotonin uptake is required for Rac1 activation in Kras‐induced acinar‐to‐ductal metaplasia in the pancreas
Enrica Saponara (2018)
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Mechanical-control of cell proliferation increases resistance to chemotherapeutic agents
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Oxidative Stress and Gastrointestinal System Cancers
Ahmet Engin Atay (2017)
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Macropinocytosis Exploitation by Cancers and Cancer Therapeutics
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Leveraging Mechanisms Governing Pancreatic Tumorigenesis To Reduce Pancreatic Cancer Mortality
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Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation.
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Phellodendrine chloride suppresses proliferation of KRAS mutated pancreatic cancer cells through inhibition of nutrients uptake via macropinocytosis
Pyone Myat Thu (2019)
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Precision Immuno-Oncology: Prospects of Individualized Immunotherapy for Pancreatic Cancer
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БИОМАРКЕРЫ, НЕОАНГИОГЕНЕЗ И ФАКТОРЫ РОСТА ПРИ РАКЕ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ
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Jia-Ren Lin (2018)
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The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and Their Role in Human Tumorigenesis
Giulia Cazzanelli (2018)
Molecular subtypes of pancreatic adenocarcinoma
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Superior efficacy of the antifungal agent ciclopirox olamine over gemcitabine in pancreatic cancer models
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Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP
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A Phase I Dose-Escalation Trial of BN-CV301, a Recombinant Poxviral Vaccine Targeting MUC1 and CEA with Costimulatory Molecules
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PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells.
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H. A. Mokhlis (2019)
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Selective targeting of an oncogenic KRAS mutant allele by CRISPR/Cas9 induces efficient tumor regression
Qianqian Gao (2019)
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