We conclude that there is substantial discordance in EGFR and K-RAS mutational status between the primary tumours and corresponding metastases in patients with NSCLC and this might have therapeutic implications when treatment with TKIs is considered.
Recent clinical data have provided substantial evidence that KRAS mutational status should be utilized as a diagnostic marker for predicting that response to anti-EGFR therapies in colorectal and non-small cell lung cancer.
Despite these advances and recent studies on the predictive value of activating EGFR mutation and KRAS mutations with response in non-small-cell lung cancer and colon cancer patients, there is currently no reliable predictive marker for response to therapy with the anti-EGFR monoclonal antibodies cetuximab and panitumumab or the small molecule EGFR tyrosine kinase inhibitors gefitinib and erlotinib.
The G(1) arrest induced by either C-RAF depletion or sorafenib in cells with mutant KRAS was associated with down-regulation of cyclin E. Our results thus suggest that sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS.
The mutation frequency of KRAS in NSCLC patients in mainland China is similar to those in East Asian countries, but lower than those in western countries.
Recent studies in metastatic colorectal cancer highlighted that somatic mutations in KRAS represent a negative predictor of response to anti-EGFR monoclonal antibodies; KRAS mutations also represent an important mechanism of resistance to TKIs in NSCLC.
We therefore screened 90 non-small cell lung carcinoma (NSCLC) samples, initially for mutations in S100A2 and then also for mutations in P53 and K-RAS genes.
We found that BEZ235 induces a striking antiproliferative effect both in transgenic mice with oncogenic K-RAS-induced NSCLC and in NSCLC cell lines expressing oncogenic K-RAS.
Because of the established importance of EGFR and K-Ras mutations in non-small cell lung cancer (NSCLC), we investigated the relationship between these mutations and EphA2 in this cancer type.
Our Review strongly suggests that KRAS mutations have no value in response prediction to conventional chemotherapy in NSCLC, CRC and other solid tumors.
Our data suggest that EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC.
The epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated with different frequencies in non-small cell lung cancer and mutations predict clinical response to EGFR inhibitors.
Ki-67 high-expressers with KRAS mutations showed an additional higher risk of recurrence compared to low-expressers without mutations (5-year DFS 37.5% vs. 93.3%, P<0.001: adjusted HR 16.82, 95% CI 3.77-74.98, P<0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC, p=0.577).
The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC.