Mutational activation of KRAS promotes various malignancies, including lung adenocarcinoma. Knowledge of the molecular targets mediating the downstream effects of activated KRAS is limited. Here, we provide the KRAS target proteins and N-glycoproteins using human bronchial epithelial cells with and without the expression of activated KRAS (KRAS). Using an OFFGEL peptide fractionation and hydraz...

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, and no targeted therapy is currently available. The aim of the present study was to investigate the prognostic significance of the expression of V-Ki-ras2 Κirsten rat sarcoma viral oncogene homolog (KRAS), downstream signaling pathway genes and the association with clinical characteristics in PDAC patients undergoing radi...

PURPOSE Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC. EXPERIMENTAL DESIGN DNA extracted from p...

Malignant gliomas can be induced in mice through the combined expression of activated forms of both KRas and Akt in glial progenitor cells. To determine the reliance of these tumors on continued KRas signaling in vivo, we generated a viral vector that allows the expression of KRas to be controlled post-delivery. Tumor-free survival rates were compared between those animals with continued KRas e...

Hypermethylation-mediated tumor suppressor gene (TSG) silencing is a central epigenetic alteration in RAS-dependent tumorigenesis. Ten-eleven translocation (TET) enzymes can depress DNA methylation by hydroxylation of 5-methylcytosine (5mC) bases to 5-hydroxymethylcytosine (5hmC). Here, we report that suppression of TET1 is required for KRAS-induced DNA hypermethylation and cellular transformat...

The development of targeted therapies for KRAS, EGFR and HER2 may increase the range of response in patients with colorectal cancer. Mutation at codons 12 and 13 of the KRAS gene has been shown to be predictive of cetuximab response in colorectal cancer. However, due to the combined effects of multiple oncogenes involved in disease progression of patients with colorectal cancer, it seems to be ...

KRAS is an attractive pancreatic ductal adenocarcinoma (PDAC) therapeutic target. E3 ligase is thought to be the component of the ubiquitin conjugation system that is directly responsible for substrate recognition. In this study, an engineered E3 ubiquitin ligase (RC-U) was generated to target the KRAS oncoprotein for ubiquitination and degradation. The engineered E3 ubiquitin ligases (RC-U) we...

INTRODUCTION Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. METHODS We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to dete...

BACKGROUND ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy. PATIENTS AND METHODS Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories...

BACKGROUND In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. METHODS We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integr...