EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

“…These results are consistent with previous data, 11 hypothesizing that p53-mutated status may be implicated in cell resistance to cetuximab.…”

“…Introduction of p53 expression resulted in a significant increase in growth inhibition and apoptosis induction, thus confirming the well-established essential function of P53 as mediator of cell growth and apoptosis control already reported in the literature with p53 gene transfer in head and neck, and pancreatic cancer cell lines. 26,27 These results are in agreement with a previous study, 11 which demonstrated that, in PTEN-deficient cells, p53 regulates cell survival by transcriptional downregulation of PIK3-CA (encoding p110 catalytic subunit of PI3K) independently of PTEN. Conversely, in pten intact cells, induction of p53 downregulates PIK3CA and increases PTEN protein expression 12 through a p53 response element located into PIK3CA promoter.…”

“…10 Previous study already demonstrated that cetuximab inhibited the growth of wild-type p53 but not of mutated p53 cancer cells and hypothesized that resistance to cetuximab could relate to p53 mutation. 11 In addition, recent study showed that induction of P53 resulted in decreased in phosphorylated AKT activity in cell line, which did not express PTEN protein, thus highlighting that p53 was involved in regulation of survival PI3K/AKT pathway in epithelial tumors, and independently of PTEN expression. 12 It was reported that activation of p53-dependent downstream targets BAX with concomitant increase of MAPKinase (MAPK) pathways leading to apoptosis.…”

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…However, initial studies did not exhibit any significant benefit of this anti-Her2/neu treatment in HCC patients (Hsu et al, 2002;Xian et al, 2005), which is in keeping with the lack of significant membranous Her2 expression in HCCs in one study (Prange and Schirmacher, 2001). In contrast, anti-EGFR/Her1/ErbB-1 antibodies such as cetuximab (erbitux) have recently been shown to inhibit cell cycle progression and induce apoptosis in HCC cells (Huether et al, 2005a).…”

Reactivation of the insulin-like growth factor-II signaling pathway in human hepatocellular carcinoma

“…Equally, IGF-Ⅱ induced tumor cell motility was reduced by picropodophyllin (Nussbaum et al, unpublished data). In addition, the inhibition of IGF-IR-signaling by a combination of AG1024 and EGF-R-signaling by RTKinhibitors or blocking antibodies synergistically reduced tumor growth [114,115] . However, NVP-ADW742 affects the viability of hepatocytes in a concentration-dependent manner.…”