|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
While CDK4/6 represents a downstream target of both KRAS mutation and loss of the CDKN2A tumor suppressor in PDAC, clinical and preclinical studies indicate that pharmacological CDK4/6 inhibitors are only modestly effective.
|
31745297 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our group previously identified the guanine nucleotide exchange factor ARHGEF10 in a genomic screen for genes with copy number alterations that may synergize with oncogenic KRAS to promote PDAC carcinogenesis.
|
31477830 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Activating KRAS mutation, occurring in >90% PDACs, is present in pancreatic intraepithelial neoplasia lesions, the precursor ductal lesions of PDAC, indicating additional genetic alterations contribute to the pathogenesis of PDAC.
|
31046123 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
According to cancer-genome sequences, > 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations.
|
31746520 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Instead, upregulated KRAS-independent PI3Kg activity was able to support macropinocytosis in KRASG12R-mutant PDAC.
|
31649109 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, in pancreatic ductal adenocarcinoma (PDAC) there are only four abundantly common driver mutations (KRAS, CDKN2A, TP53, and SMAD4), which are not currently actionable.
|
31639254 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms.
|
31352001 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We developed an approach to statistically humanize the mouse networks with data from human cancer and identified genes within the humanized CRC and PDAC networks synthetically lethal with mutant KRAS.
|
31521603 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Obesity driven by chronic consumption of high-fat diet (HFD) is a major risk factor for oncogenic KRAS-mediated pancreatic ductal adenocarcinoma (PDAC).
|
30819189 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In conclusion, we provide the first evidence that miR-873 acts as a tumor suppressor by targeting KRAS and that miR-873-based gene therapy may be a therapeutic strategy in PDAC and TNBC.
|
30654191 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the current study, we demonstrate that ISG15 pathway knockdown reverses the KRAS-associated phenotypes of PDAC cells such as increased proliferation and colony formation.
|
31709456 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Pancreatic juice from PDAC patients is rich in KRAS mutations often not seen in the primary tumor and possibly reflecting precancerous lesions in other regions of the pancreas.
|
30611220 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the context of pancreatic ductal adenocarcinoma (PDAC), oncogenic KRAS induces benign pancreatic intraepithelial neoplasias (PanINs), which exhibit features of oncogene-induced senescence.
|
30614183 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
KRAS mutations play a critical role as they are involved in both initiating and maintaining PDAC development.
|
31341034 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
KRAS mutations are present in >90% of PDAC and are connected to many signaling pathways through its oncogenic cascade, including extracellular regulated kinase (ERK) and MYC.
|
30228208 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we develop an unbiased, functional target-discovery platform to query KRAS*-dependent changes of the PDAC surfaceome, which reveals syndecan 1 (SDC1, also known as CD138) as a protein that is upregulated at the cell surface by KRAS*.
|
30918400 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In summary, we conclude that albumin conjugation is an exploitable drug delivery strategy that significantly opens the therapeutic windows of otherwise undevelopable anti-cancer agents for KRAS-mutant PDAC therapy, and creates a new landscape for clinical evaluation and future translation of such compounds.
|
30653981 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Thereby, current sequencing studies recapitulate this genetic heterogeneity in PDAC and show besides a handful of driver mutations (KRAS, TP53) a plethora of passenger mutations that allow to define subtypes.
|
31236113 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
IQ motif containing GTPase-activating protein 1 (IQGAP1) acts as a scaffold for aberrant mitogen-activated protein kinase (MAPK) signaling driven by KRAS mutations in pancreatic ductal adenocarcinoma (PDAC).
|
30540680 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
KRAS driver mutations occur in approximately 95% of PDAC cases and cause the activation of several signaling pathways such as mitogen-activated protein kinase (MAPK) pathways.
|
30982078 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Of importance is identifying the subgroup of KRAS -wild type PDAC (approximately 5%) where there is enrichment for targetable opportunities.
|
30927677 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Initially we found that miR-217, which has been shown to directly regulate KRAS expression, is downregulated in our PDAC samples, thus we tested the benefits of anti-miR-21, miR-217 mimic or siKRAS loaded into the tumor-penetrating nanoparticles (TPN) that we had previously shown to potently target the largely impenetrable PDAC tumors, and found an enhanced anti-tumoral response upon dual treatments in KRAS-mutated PDAC models.
|
31523393 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Additional genetic mutations and/or environmental, nutritional, and metabolic stressors, e.g. inflammation and obesity, are required for efficient PDAC formation with activation of KRAS downstream effectors.
|
29079305 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Thus, measurement of cellular reactive oxygen species (ROS) levels is essential to determine how oxidative stress affects mutant KRAS and modulates intracellular signaling pathways leading to the change of cellular functions and the development of PDAC.
|
30378057 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recent evidence suggests that phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1) are key effectors of oncogenic KRAS in PDAC.
|
31088502 |
2019 |