Mostly, we verified a higher frequency rate of the KRAS(G13) and EGFR A13_del oncogene mutations in right colon cancer; whereas KRAS(G12) codon mutation occurs more frequently in left colon cancers.
In conclusion, detection of somatic mutations in the epidermal growth factor receptor may play an important role in predicting sensitivity to gefitinib in colon cancer.
Through biochemical and cellular pharmacologic studies, we have determined that cells harboring the colon cancer-derived G719S and G724S mutants are responsive to cetuximab therapy in vitro and found that the requirement for asymmetric dimerization of these mutant EGFR to promote cellular transformation may explain their greater inhibition by cetuximab than small-molecule kinase inhibitors.
Panitumumab affects colon cancer cell proliferation independently of KRAS mutations and EGFR protein levels, possibly through the induction of autophagy.
The paradigms are EGFR mutations in adenocarcinoma of the lung that can be treated with gefitinib, KRAS mutations in colon cancer with respect to treatment with EGFR antibodies, and the use of gene-expression analysis for ER-positive, node-negative breast cancer patients with respect to chemotherapy options.
Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors.
Most BRAF (V600E) mutant melanomas are sensitive to selective BRAF inhibitors, but BRAF mutant colon cancers are intrinsically resistant to these drugs because of feedback activation of EGFR.
The results of these studies suggest that combined treatment of BRAF(V600E)-driven colon cancers with both vemurafenib and EGFR inhibitors is worth clinical evaluation.
Mutations at the K-RAS locus in colon cancer cells are frequently associated with lack of responsiveness to therapy with EGFR inhibitors, as a consequence of the activation of Ras-dependent intracellular signals.
In conclusion, caveolin-1 is more expressed in cancer tissues than normal colon and related with Akt-1, not with EGFR expression in colorectal cancer tissues, which suggests that signaling for caveolin-1 affects Akt-1 activation, but this reaction is not initiated by EGFR stimulation in colon cancer.
In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients.
Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388).
In order to define proteins involved in potential resistance mechanisms, we examined the effect of gefitinib (ZD1839, Iressa) in the EGFR-positive colon cancer cell lines Caco-2, DiFi, HRT-18 and HT-29.
To the best of our knowledge, anti-cancer activity of this chimeric protein against colon cancer that overexpresses epidermal growth factor receptor (EGFR) has not yet been studied.
Interaction of EGFR and ERCC1 might correlate with radiation-induced DNA damage when p53 mutant colon cancer cell lines are exposed to 5-FU followed by radiation.
To examine whether erlotinib gives similar results to gefitinib, a small molecule epidermal growth factor receptor (HER1/EGFR) tyrosine kinase (TK) inhibitor that inhibits the growth of human bladder cancer cell lines in vitro, and given that interferon-alpha (IFNalpha) promotes an antiproliferative effect of HER1/EGFR inhibitors on colon cancer cell lines, to also determine the effects of erlotinib alone or together with INFalpha on bladder cancer cell lines, and whether sensitivity is influenced by HER1/EGFR mutation status.
Epidermal growth factor receptor status and persistent activation of Akt and p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and colon cancer cell lines.
In the present study, we investigated the effects of bile acids on cell signaling and proliferation of a human colon cancer cell line (H508 cells) that abundantly expresses M3R and EGFR.