Blockade of epidermal growth factor receptor (EGFR) activity

Jimeno, Antonio; Hidalgo, Manuel

doi:10.1016/j.critrevonc.2004.10.005

Cited by 25 publications

(23 citation statements)

References 81 publications

(92 reference statements)

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“…Autocrine growth stimulation of DU145 cells by EGF/TGFα is well doc- umented [12,13,17]. However, it has been shown that an acquired resistance to inhibitors of EGFR has been reported clinically [42]. It has been suggested that the resistance is associated with increased signaling through the IGFI receptor [35].…”

Section: Discussionmentioning

confidence: 99%

The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

Kisielewska

Ligeza²,

Klein³

2008

Folia Histochem Cytobiol.

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Abstract:It is well established that autocrine growth of human prostate cancer cell line DU145 is dependent on TGF (EGF)/EGFR loop. However, the participation of several other growth factors in proliferation of DU145 cells has been also proposed. We employed two selective tyrosine kinase inhibitors (tyrphostins): AG1024 (an IGFIR inhibitor) and SU1498 (a VEGFR2 inhibitor) for growth regulation of DU145 cells, cultured in chemically defined DMEM/F12 medium. Both the tested compounds inhibited autocrine growth of DU145 cells at similar concentration values (IC50 ≈2.5 μM). The tyrphostins arrested cell growth of DU145 in G1 phase, similarly as inhibitors of EGFR. However, in contrast to selective inhibitors of EGFR, neither AG1024, nor SU1498 (at concentration ≤10 μM) decreased the viability of the investigated cells. These results strongly suggest that autocrine growth of DU145 cells is stimulated by, at least, three autocrine loops: TGFα(EGF)/EGFR, IGFII/IGFIr and VEGF/VEGFR2(VEGFR1). These data support the hypothesis of multi-loops growth regulation of metastatic prostate cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

Kisielewska

Ligeza²,

Klein³

2008

Folia Histochem Cytobiol.

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“…First of all, it is overexpressed in most of the tumours from NSCLC and HNC patients. This overexpression, ultimately causing increased proliferation or cell motility, and decreased apoptosis (Jimeno and Hidalgo, 2005), has been related to the progression of the tumour. Another appealing reason is the fact that new approved therapies for those cancers are targeting EGFR, based on the inhibition of its TK activity (Baselga, 2002;Jimeno and Hidalgo, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, tumours that overexpress the EGFR have been challenged with the anti-EGFR therapies currently approved (Jimeno and Hidalgo, 2005;Mendelsohn and Baselga, 2006). In addition to the traditional tissue-based analysis, there is an evident interest on the evaluation of the serum levels of the EGFR and its ligands, not only because they could indicate the presence of the malignancy but for their potential utility in the follow-up of patients, especially those receiving anti-EGFR therapies.…”

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confidence: 99%

“…Analysis of tumour levels of the EGFR as assayed by immunohistochemistry or in tumour lysates has shown that its overexpression is correlated with disease progression, poor survival and development of resistance to cytotoxic agents, being involved in over 70% of all cancers (Baselga, 2002;Jimeno and Hidalgo, 2005), specially in non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). Recently, tumours that overexpress the EGFR have been challenged with the anti-EGFR therapies currently approved (Jimeno and Hidalgo, 2005;Mendelsohn and Baselga, 2006).…”

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confidence: 99%

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Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma

et al. 2007

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Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-a (TGF-a) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we found sEGFR and EGF levels significantly lowered in patients with respect to healthy donors. In HNC patients, significantly diminished levels were found in the case of sEGFR, EGF and also AR. In both malignancies, no significant association was found between the serum levels of the molecules and the patients' gender, age or smoking habit. Only a significant association was found between the decrease of sEGFR and the absence of distant metastasis in NSCLC and the tumour stage in HNC. The most interesting result was that combining sEGFR and EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing specificity (97.8% in both cases). The use of discriminant analysis and logistic regression improved the sensitivity for NSCLC and the specificity for HNC. These data demonstrate a potentially interesting value of the serum levels of sEGFR and EGF, especially when combined, as markers for NSCLC and HNC.

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“…Clinical trials using EGFR inhibitors, such as erlotinib, have shown partial responses or stabilization in various types of EGFR-positive tumors, with relatively mild side effects (1,2).…”

Section: Introductionmentioning

confidence: 99%

Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts

Birle

Hedley²

2006

Molecular Cancer Therapeutics

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Clinical trials using rapamycin analogues or HER1/epidermal growth factor receptor (EGFR) inhibitors show that each class of agent has activity against a range of human solid tumors. Because blockade of mitogen-activated protein kinase signaling occurs following HER1/EGFR inhibition in some cell types, we tested the combination of rapamycin and erlotinib in SiHa, Me180, and CaSki human cervical carcinomas xenografts in severe combined immunodeficient mice. In tissue culture, all three cell lines showed decreased phosphorylated S6 ribosomal protein and decreased phosphorylated extracellular signal-regulated kinase (ERK) following treatment with rapamycin and erlotinib, respectively. In SiHa tumors, suppression of phosphorylated S6 was induced by either drug alone, whereas phosphorylated ERK decreased with erlotinib, and enhancement of these effects was obtained with the combination. Continuous treatment of xenografts for 3 weeks led to significant tumor growth delay compared with vehicle control for rapamycin as single agent (P = 0.003) and greater for the combination (P = 0.04 versus rapamycin). Significant antiangiogenic effect was obtained in SiHa xenografts using the drugs together (measured by microvascular density and vascular endothelial growth factor plasma levels) but not for the single agents. Me180 and CaSki xenografts showed significant growth delay with rapamycin but not with erlotinib. Erlotinib treatment resulted in decreased phosphorylated ERK, associated with enhanced suppression of phosphorylated S6 and improved growth delay in Me180 but not in CaSki tumors. These results support the further clinical investigation of rapamycin and EGFR inhibitor combinations in anticancer therapy but highlight the problem of intertumoral heterogeneity in the prediction of in vivo response.

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Blockade of epidermal growth factor receptor (EGFR) activity

Cited by 25 publications

References 81 publications

The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma

Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts

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