KRAS mutant colorectal cancer (CRC) patients develop lung and brain metastases more frequently than KRAS wild-type (WT) counterpart. We retrospectively investigated the prognostic role of KRAS, BRAF, and PIK3CA (exon 20) mutations and loss of phosphatase and tensin homolog (PTEN) in surgically resected lung metastases. Lung specimens from 75 metastatic CRC (mCRC) patients treated with one or mo...

KRAS mutations in NSCLC are supposed to indicate a poor prognosis and poor response to anticancer treatments but this feature lacks a mechanistic basis so far. In tumors, KRAS was found to be mutated mostly at codons 12 and 13 and a pool of mutations differing in the base alteration and the amino acid substitution have been described. The different KRAS mutations may differently impact on cance...

The most challenging task in colorectal cancer research nowadays is to understand the development of acquired resistance to antiEGFR drugs. The key reason for this problem is the KRAS mutations produced after the treatment with monoclonal antibodies (mAb). KRAS screening tests done before the start of the treatment are not very sensitive to identify minute quantity of the mutated cells, which c...

PURPOSE This study is aimed to identify genes within the KRAS genomic amplicon that are both coupregulated and essential for cell proliferation when KRAS is amplified in lung cancer. EXPERIMENTAL DESIGN We used an integrated genomic approach to identify genes that are coamplified with KRAS in lung adenocarcinomas and subsequently preformed an RNA interference (RNAi) screen to uncover function...

Objective(s): The rs712 polymorphism in a let-7 microRNA-binding site at KRAS gene has been associated with cancer. To examine its association with rs712 polymorphism, we analyzed Mexican individuals with colorectal cancer (CRC) and healthy subjects. Materials and Methods: Genotyping of the rs712 polymorphism was performed by polymerase chain reaction in 281 controls and 336 CRC patients. Resul...

Multiple RNA-binding proteins and non-coding RNAs, such as microRNAs (miRNAs), are involved in post-transcriptional gene regulation through recognition motifs in the 3' untranslated region (UTR) of their target genes. The KRAS gene encodes a key signaling protein, and its messenger RNA (mRNA) contains an exceptionally long 3' UTR; this suggests that it may be subject to a highly complex set of ...

No effective targeted therapies exist for cancers with somatic KRAS mutations. Here we develop a synthetic lethal chemical screen in isogenic KRAS-mutant and wild-type cells to identify clinical drug pairs. Our results show that dual inhibition of polo-like kinase 1 and RhoA/Rho kinase (ROCK) leads to the synergistic effects in KRAS-mutant cancers. Microarray analysis reveals that this combinat...

CXCL8, a ligand for the chemokine receptor CXCR2, was recently reported to be a transcriptional target of Ras signaling, but its role in Ras-induced tumorigenesis has not been fully defined. Here, we investigated the role of KC and MIP-2, the murine homologues of CXCL8, in Kras(LA1) mice, which develop lung adenocarcinoma owing to somatic activation of the KRAS oncogene. We first investigated b...

The KRAS mutation test is recommended that it may determine which patients with advanced colorectal or lung cancer are eligible for antiEGFR targeted therapies. Traditional molecular techniques such as polymerase chain reaction (PCR) combined direct sequencing are limited by the difficulty of obtaining patients’ cancer tissues for analysis. Finding an alternative method to detect KRAS gene muta...

Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expres...