The indole-aminoquinazoline hybrids compounds <b>4f</b> and <b>4g</b> induced apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC<sub>50</sub> = 52.5 nM) and significant (IC<sub>50</sub> = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR) against gefitinib (IC<sub>50</sub> = 38.9 nM).
Eligible patients were aged 20 years or older; had histologically confirmed unresectable, metastatic colorectal adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumours with wild-type KRAS); and had no previous treatment with regorafenib.
Targeted therapies using the anti-EGFR antibodies panitumumab (Pmab) or cetuximab (Cmab) are currently restricted to patients with metastatic colorectal adenocarcinoma whose tumours do not show a mutation in KRAS.
The involvement of the epidermal growth factor receptor (EGFR) pathway in colorectal adenocarcinoma oncogenesis is well established, and the same is expected to apply to ITACs.
EGFR gene copy number gains and KRAS/BRAF mutations have been reported to act as positive and negative predictors, respectively, of therapeutic response to EGFR targeted therapies in colorectal adenocarcinoma, a tumour type claimed to be genetically similar to ITAC.
Cetuximab is an anti-epidermal growth factor receptor that helps effectively treat patients with advanced colorectal adenocarcinoma without KRAS activating mutations.
To assess and compare immunohistochemical expression of epidermal growth factor receptor (EGFR) with gene amplification as demonstrated by chromogenic in situ hybridisation (CISH), in colorectal adenocarcinoma.
Immunohistochemical detection of expression of the epidermal growth factor receptor (EGFR) has been utilized to identify eligible patients with solid malignant tumors, including colorectal adenocarcinoma, for monoclonal antibody therapy (eg, cetuximab).