Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 177 for “"KRAS"”.
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Modulation of Kras Structure and Dynamics By Kras Ubiquitination and Membrane Depolarization
<p>KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS …
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Oncogenic Kras and Telomere Biology In Crc Progression
… CRCs carrying oncogenic mutations in the <em>KRAS</em> oncogene, henceforth referred to as KRAS*, exhibit a 25% higher propensity for developing liver metastases. Similarly, in our CRC mouse model, engineered with an inducible <em>Kras</em>* transgene and conditional null alleles of …
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The Role of METTL21A in Kras-driven Cancers
… and crossed to PDAC models: p48<sup>Cre/+</sup> Kras<sup>G12D/+</sup>(<em>Kras </em>vs. <em>Kras; Mettl21a</em>) and <em>p48<sup>Cre/+</sup>; Kras<sup>G12D/+</sup>; p53<sup>fl/fl</sup> </em>(<em>Kras; p53 </em>vs. <em>Kras;p53</em>; <em>Mettl21a</em>), and LUAC models:Kras<sup>G12D/+</sup> …
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Structure Based Drug Design of High Affinity Kras Inhibitors
… three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules that bind to mutant KRAS, we conducted a high-throughput virtual screen of drug-like compounds against a previously …
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Targeting Plasma Membrane Phosphatidylserine Content to Inhibit Oncogenic Kras Function
<p>The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). …
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Interactions between IP3 receptor and Kras-induced actin-interacting protein
… 'licensing,' involving the association with Kras-induced actin-interacting protein (KRAP). The immobility of the licensed IP3R fraction is attributed to its interaction with KRAP, which anchors IP3R to actin filaments near plasma membrane (PM)-ER junctions. Given the reported upregulation of …
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Cd47+ Exosomes Facilitate Effective Targeting of Oncogenic Kras In Pancreatic Cancer
… of PDAC show that mutations in the GTPase KRAS are encountered in the majority of patients that present with the disease, and are key drivers of cancer initiation, progression and metastasis. However, while it is recognized that the Ras mediated signaling pathway is a key mediator of PDAC …
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Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms
… mutated gene in PDAC, the oncogene <em>KRAS</em>, remains largely undruggable, except for <em>KRAS<sup>G12C</sup> </em>mutations, which may be inhibited by sotorasib. Activating mutations in the oncogene <em>KRAS</em> are believed to be the earliest genetic mutation in the development of …
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Investigating the Role of Oncogenic KRAS G12 Mutations in Cell Signalling
… most frequently mutated oncogene in cancer is KRAS, encoding a small GTPase protein involved in controlling the activity of critical signalling pathways that regulate normal cellular proliferation, such as the PI3K and ERK pathways. The prevalence of different codon substitutions in the KRAS …
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Investigating the requirement of KRAS for the maintenance of pancreatic cancer
… have identified mutations in the proto-oncogene KRAS as a hallmark of PDAC, making KRAS an attractive therapeutic target. While the driver role of oncogenic KRAS for PDAC initiation has been well established, the degree of KRAS oncogene addiction in established PDAC tumors remains unclear. To …
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Assessing the Mutational Landscape of BRAF- and KRAS-Wild Type Colorectal Cancer
… are driven by activating mutations in KRAS or BRAF oncogenes. However, the other 50% of colorectal cancer cases are wild type for both genes; thus identification and characterization of the landscape of mutations in non-BRAF and KRAS-mutated colorectal cancer is helpful to propose …
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Identification of Oncogenic KRAS-Associated Vulnerabilities in Non-Small Cell Lung Cancer
Activating mutations in KRAS are frequently involved in the pathogenesis of non-small cell lung cancer (NSCLC), the disease responsible for the most cancer-related deaths in the US. Despite intensive efforts to develop drugs that directly interfere with KRAS activity over the past decade, no …
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Targeting Stromal-Mediated Resistance Mechanisms in Oncogenic KRAS-Driven Pancreatic Ductal Adenocarcinoma
… of the most lethal malignancies, with oncogenic KRAS mutations driving both tumor initiation and maintenance. Despite recent breakthroughs in KRAS-targeted therapies, the rapid emergence of resistance mechanisms limits their clinical efficacy. This dissertation investigates three interconnected …
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Impact of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer
… Mutations in <em>KRAS/NRAS</em> (<em>RAS</em>) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to …
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Evaluation of Altered Kras Codon Bias and NOS Inhibition During Lung Tumorigenesis
… GTPases <italic>HRAS, <italic>NRAS and <italic>KRAS are mutated in approximately one-third of all human cancers, rendering the proteins constitutively active and oncogenic. Lung cancer is the leading cause of cancer deaths worldwide, and more than 20% of human lung cancers harbor mutations in …
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PROTEINi screens identify ORP9 as a novel regulator of KRAS-driven signalling
KRAS is one of the most frequently mutated proteins in cancer, driving the excessive activation of the downstream RAF-MEK-ERK cascade, alongside additional pathways that promote cellular proliferation, survival and migration. KRAS traffics to the plasma membrane in order to be activated and bind to …
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Whole body metabolic alterations as an early event in Kras-Driven cancers
Cancer is a disease defined by the uncontrolled proliferation of cells. Using primarily in vitro approaches, researchers have gained critical insight into how different oncogenic mutations alter the regulation of metabolic pathways and shape nutrient utilization to facilitate the acquisition and …
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Regulation of the kRAS Promoter in Pancreatic Cancer by Proteins and Small Molecules
… regulate the expression of their target genes. kRAS is a proto-oncogene with intrinsic GTPase activity, that contributes to cell proliferation, division, and apoptosis. kRAS mutations are observed in >95% of pancreatic adenocarcinoma and in 30 % of all human tumors. Pancreatic cancer is the …
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