In sporadic colorectal cancer (CRC), the BRAFV600E mutation is associated with deficient mismatch repair (MMR) status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR) CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR) CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination w...

BACKGROUND In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on p...

The KRAS-variant is a biologically functional, microRNA binding site variant, which predicts increased cancer risk especially for women. Because external exposures, such as chemotherapy, differentially impact the effect of this mutation, we evaluated the association of estrogen exposures, breast cancer (BC) risk and tumor biology in women with the KRAS-variant. Women with BC (n = 1712), the sub...

KRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the Kras G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic...

In this study, we evaluated the clinical utility of detecting KRAS mutations in circulating cell-free (ccf)DNA of metastatic colorectal cancer patients. We prospectively recruited 94 metastatic colorectal cancer patients. Circulating cell-free DNA was extracted from plasma samples and analyzed for the presence of seven KRAS point mutations. Using the Invader Plus assay with peptide nucleic acid...

Oncogenic KRAS is found in more than 25% of lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC), and is an important target for drug development. To this end, we generated four NSCLC lines with stable knockdown selective for oncogenic KRAS. As expected, stable knockdown of oncogenic KRAS led to inhibition of in vitro and in vivo tumor growth in the KRAS-muta...

KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. M...

colorectal cancer (crc) metastasis to the thyroid gland is rare. here wereport a 45 yr-old man in western iran referred to hematology clinic, kermanshah city, iran in march 2014 with complaint of exertional dyspnea, multi-nodular goiter as well as complaint of exertional dyspnea, and multi-nodular goiter. his history included a low anterior resection of rectum in 9 months ago for a high-risk st...

Oncogenic KRAS is found inmore than 25% of lung adenocarcinomas, the major histologic subtype of non– small cell lung cancer (NSCLC), and is an important target for drug development. To this end, we generated four NSCLC lines with stable knockdown selective for oncogenic KRAS. As expected, stable knockdown of oncogenic KRAS led to inhibition of in vitro and in vivo tumor growth in the KRAS-muta...

KRAS mutations are proved as a predictor of response to EGFR-targeted therapies for patients with metastatic colorectal cancer. For identifying the wild-type KRAS (wt-KRAS) responder subset of patients who will benefit from novel agents our laboratory has introduced the TheraSreen K-RAS Mutation Kit(R) an allele-specific RT-PCR based assay. Our aim is to describe the validation procedure of thi...