Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.
To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients.
KRAS mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care (BSC).
It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear.
Of 68 retrieved manuscripts reporting on anti-EGFR monoclonal-antibody-based treatment of mCRC, eight studies were deemed eligible for the final analysis (306 of 817 patients with mutated k-RAS).
Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients.
KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.
We investigated the association of FcgammaR polymorphisms and KRAS mutation with the outcome of irinotecan-refractory mCRC patients treated with cetuximab plus irinotecan.
Here, we present the mutational analysis of PIK3CA and KRAS and evaluation of the PTEN protein status in a cohort of 110 patients with mCRC treated with anti-EGFR moAbs.
The presence of the KRAS mutations in metastatic colorectal cancer patients correlates with lack of response to the certain epidemal growth factor receptor (EGFR) inhibitor therapies, such as Panitumumab and Cetuximab.
We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab.
Although there is still some debate regarding the prognostic importance of KRAS mutations in patients with metastatic colorectal cancer, several recent phase 2 and 3 studies have identified the presence of mutations at codons 12 and 13 of KRAS as predictors of poor response to the anti-EGFR monoclonal antibodies panitumumab and cetuximab.
It has been reported that activating KRAS mutations negatively affect response to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer.
A cohort of patients with irinotecan-refractory mCRC who were treated with cetuximab plus irinotecan was tested for PTEN immunoreactivity (ie, immunohistochemistry; IHC), pAKT IHC, and KRAS mutations.
A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer.
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.
Because of this compelling data, the National Comprehensive Cancer Network and the American Society of Clinical Oncology have recommended determination of KRAS mutation status in all patients with metastatic colorectal cancer who are candidates for anti-EGFR therapy.
Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer.
We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC).