Methods Firefly assay targeting KRAS/NRAS/BRAF/PIK3CA was evaluated using cell-free DNA (cfDNA) reference standards and cfDNA samples from 184 mCRC patients.
Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor.
Taken together, the superior antitumor efficacy of GC1118 alone or in combination with PI3K/mTOR/AKT inhibitors shows great therapeutic potential for the treatment of <i>KRAS</i>-mutant mCRC with elevated ratios of high- to low-affinity EGFR ligands and PI3K-AKT pathway activation.
Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA-wild-type Metastatic Colorectal Cancer: The AGITG Randomized Phase II ICECREAM Study.
Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer.
PI3K/Akt/mTOR Signaling and Plasma Membrane Proteins Are Implicated in Responsiveness to Adjuvant Dendritic Cell Vaccination for Metastatic Colorectal Cancer.
Of the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer.
Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: Comparison to ctDNA and tissue in metastatic colorectal cancer.
Although epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) cetuximab are used widely to treat KRAS wild-type metastatic colorectal cancer (mCRC), patients become resistant by various mechanisms, including KRAS, BRAF, and PIK3CA mutations, thereafter relapsing.
We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012.
A retrospective observational study of clinicopathological features of KRAS, NRAS, BRAF and PIK3CA mutations in Japanese patients with metastatic colorectal cancer.
Here we report the first case of a mCRC patient whose disease had progressed on standard lines of treatment and for which we devised a personalized therapeutic approach consisting of vemurafenib (Zelboraf) and panitumumab (Vectibix), based on the following molecular profile: BRAF(V600E)-mutant, amplified EGFR (double positive) and WT KRAS, WT PIK3CA, not-amplified HER2 (triple negative).
Analysis of PTEN, BRAF and PI3K status for determination of benefit from cetuximab therapy in metastatic colorectal cancer patients refractory to chemotherapy with wild-type KRAS.
The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF-mutant mCRC.
Meta-analysis suggests that mutations in KRAS exons 3 and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer.
The EWG encourages further studies of the potential value of testing in patients with mCRC who were found to have tumors that are wild type (mutation negative) for KRAS to predict responsiveness to therapy.The EWG found insufficient evidence to recommend for or against testing for mutations in NRAS, or PIK3CA, and/or loss of expression of PTEN or AKT proteins.
Studies investigating the association of PIK3CA mutations with clinical survival outcomes of mCRC patients treated with anti-EGFR mAbs were systematically identified.
To model PIK3CA-activating mutations in late stages of cancer, we took advantage of the isogenic conversion of a PIK3CA-wild-type tumor into a PIK3CAH1047R-mutated tumor using the highly metastatic colorectal cancer cell line SW48.
These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of worseoutcomes in KRAS wild-type mCRC treated with anti-EGFR MoAbs [corrected].
Clinical usefulness of KRAS, BRAF, and PIK3CA mutations as predictive markers of cetuximab efficacy in irinotecan- and oxaliplatin-refractory Japanese patients with metastatic colorectal cancer.