Receptor tyrosine kinases as targets for anticancer drugs

Zwick, Esther; Bange, Johannes; Ullrich, Axel

doi:10.1016/s1471-4914(01)02217-1

Cited by 227 publications

(146 citation statements)

References 44 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…Over recent years, therapeutic approaches based on compounds selectively targeting oncogenic RTKs, to which cells are dependent, have been developed. 3 However, the success of these strategies has been limited since inhibition of the 'primary RTK addiction' triggers a selective pressure to acquire resistance through RTK switching. 4 As RTKs share several effectors that participate in the oncogenic process and in drug response, 5 an alternative strategy would rely on the identification of druggable signals required for RTK-triggered tumorigenesis.…”

mentioning

confidence: 99%

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

et al. 2011

View full text Add to dashboard Cite

The simplicity of BCR-ABL 'oncogene addiction' characterizing leukemia contrasts with the complexity of solid tumors where multiple 'core pathways', including receptor tyrosine kinases (RTKs) and p53, are often altered. This discrepancy illustrates the limited success of RTK antagonists in solid tumor treatment compared with the impact of Imatinib in BCR-ABL-dependent leukemia. Here, we identified c-Abl as a signaling node interconnecting Met-RTK and p53 core pathways, and showed that its inhibition impairs Met-dependent tumorigenesis. Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation on Ser(392) and Mdm2 upregulation. We found a clinical correlation between activated Met, phospho-p53, and Mdm2 levels in human tumors, supporting the role of this path in tumorigenesis. Our findings introduce the concept that RTK-driven tumors may be therapeutically treated by hitting signaling nodes interconnecting core pathways. Moreover, they underline the importance of evaluating the relevance of c-Abl antagonists for combined therapies, based on the tumor signaling signature.Cell Death and Differentiation advance online publication, 1 April 2011; doi:10.1038/cdd.2011.23

show abstract

mentioning

confidence: 99%

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Among the recent advances in the molecular targeted therapy of cancer, the applications focused on EGFR are currently the most promising and the most advanced at clinical level (Arteaga, 2001;Baselga, 2001;Ciardiello and Tortora, 2001;Yarden, 2001;Mendelsohn, 2002;Zwick et al, 2002). Considering the set of therapeutic tools targeting EGFR (Modi and Seidman, 2002), there are at present two well-identified emerging categories of drugs, the one characterised by monoclonal antibodies (Mabs) and the other by tyrosine kinase inhibitors (TKIs).…”

mentioning

confidence: 99%

Epidermal growth factor receptor double targeting by a tyrosine kinase inhibitor (Iressa) and a monoclonal antibody (Cetuximab). Impact on cell growth and molecular factors

2005

View full text Add to dashboard Cite

Among the recent advances in the molecular targeted therapy of cancer, the applications focused on epidermal growth factor receptor (EGFR) are currently the most promising and the most advanced at clinical level. In view of the different modes of action of monoclonal antibodies and tyrosine kinase inhibitors (TKI), it is tempting to examine the effect of a combination between these two EGFR targeting approaches. It was the purpose of the present study to test this combination at experimental level by using two epidermoid human cell lines CAL 33 and CAL 39. As C225 (Cetuximab s ) and ZD1839 (Iressa s ) are, respectively, the most clinically advanced drugs in the category of anti-EGFR drugs, the experiments were performed using these two representative compounds. The combination of C225 and ZD1839 was antagonistic whatever the cell line considered. These antagonistic effects were corroborated by molecular changes in apoptosis (PARP) and EGFR signalling (phospho-p42 -44). Drugs alone led to a diminution in EGFR levels, while their combination increased the cellular expression in EGFR. These data suggest that new and tempting treatment strategies on the EGFR target consisting in a double hit with a monoclonal antibody and a TKI must be considered with caution.

show abstract

“…The significance of targeting RTK signaling has been successfully demonstrated with a large number of FDA approved drugs in clinics [1,28]. In CRC monoclonal antibodies targeting RTKs are against VEGF (Bevacizumab) and EGFR (Cituximab and Panitumumab) [57].…”

Section: Therapeutic Targeting Of Ron Kinasementioning

confidence: 99%

“…Thus targeting RON is expected to have significant therapeutic efficacy in limiting the spread of metastatic CRC. Several RTK inhibitors have proven their success clinically in the past further encouraging the studies on the therapeutic utilization of RON RTK [1,27,28]. The characteristics of RON such as high prevalence in CRC and cell-surface RTK activity make it an important candidate for anti-cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

RON - The Con in Colorectal Carcinoma

Tarang

Wang²

2012

TOCOLCJ

View full text Add to dashboard Cite

Abstract:The recepteur d'origine nantais (RON) is a member of MET family of receptor tyrosine kinase (RTKs), an overexpression of which has been observed in several cancers. The expression of RON gene is required during embryonic development and also plays critical roles in regulating macrophage inflammatory response. In CRC, the overexpression of moderate RON activity contributes to their oncogenic potential by regulating several key processes such as proliferation, motility and resistance to apoptosis. Interestingly, an aberrant RON expression is often associated with the generation of several splice variants with unique transforming activities. The targeting of RON signaling pathway by the use of monoclonal antibodies and small-molecule inhibitors has shown promising therapeutic results in animal models. The present article aims at summarizing the current understanding of RON kinase in CRC.

show abstract

Receptor tyrosine kinases as targets for anticancer drugs

Cited by 227 publications

References 44 publications

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

Epidermal growth factor receptor double targeting by a tyrosine kinase inhibitor (Iressa) and a monoclonal antibody (Cetuximab). Impact on cell growth and molecular factors

RON - The Con in Colorectal Carcinoma

Contact Info

Product

Resources

About