Signal transduction pathways: New targets in oncology

Sweeb, R. K.; Beijnen, Jos H.

doi:10.1007/bf01871124

Cited by 5 publications

(6 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tyrosine analogs can also be used to bind the receptors and inhibit growth factor binding. The octapeptide somatostatin and its analogs were found to decrease the growth of cancer cells by activating tyrosine phosphatase which dephosphorylates and 'turns off' the growth signal [176]. The active site of the PTK enzymes can be divided into the Mg-ATP complex-binding site and the peptide-or protein-binding site [176].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…The octapeptide somatostatin and its analogs were found to decrease the growth of cancer cells by activating tyrosine phosphatase which dephosphorylates and 'turns off' the growth signal [176]. The active site of the PTK enzymes can be divided into the Mg-ATP complex-binding site and the peptide-or protein-binding site [176]. The initial PTK inhibitors were natural products, such as quercetin, genistein, lavendustin A, erbstatin, herbimycin A, and others which are mostly bound to the ATP-binding site and, consequently, exhibit a broad but nonspecific inhibition of the tyrosine kinases [182].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…The alkaloid staurosporine (42a) was found to exert an inhibitory activity against PKC [230,231], even though it is a non-specific protein kinase inhibitor, whereas the 7-hydroxy analog (42b) of staurosporine has a more selective anticancer activity in vivo against PKC [232]. Other specific PKC inhibitors include compounds of various origin, e. g., calphostin C, sphingolipids, the nucleoside analog sangivamycin, cationic lipids such as sphingosine and its derivatives, dequalinium, and ether lipid analogues such as edelfosine (43) [169,172,174,176]. These compounds were found to inhibit PKC and the enzymes phospholipase C (PLC) and phosphatidylinositol 3¢ (PI 3¢) kinase [169,176].…”

Section: Protein Kinase Inhibitorsmentioning

confidence: 99%

“…Other specific PKC inhibitors include compounds of various origin, e. g., calphostin C, sphingolipids, the nucleoside analog sangivamycin, cationic lipids such as sphingosine and its derivatives, dequalinium, and ether lipid analogues such as edelfosine (43) [169,172,174,176]. These compounds were found to inhibit PKC and the enzymes phospholipase C (PLC) and phosphatidylinositol 3¢ (PI 3¢) kinase [169,176]. Tamoxifen (44), a drug already in clinical application as an antiestrogen was shown to inhibit PKC at high doses [174,175,233].…”

Section: Protein Kinase Inhibitorsmentioning

confidence: 99%

See 3 more Smart Citations

Critical appraisals of approaches for predictive designs in anticancer drugs

Gnewuch

Sosnovsky

2002

Cellular and Molecular Life Sciences (CMLS)

View full text Add to dashboard Cite

The present review provides a critical appraisal of the most important areas in cancer drug research and, ultimately, in clinical oncology and therapy, with emphasis on the elucidation of possible predictive designs for the development of new anticancer drugs. These assessments encompass the well-established anticancer drugs and congeners which have been employed over the years in clinical therapy, and the more recent exploratory agents still requiring further rigorous scrutiny in the clinical environment. These areas mainly include the bioreversible redox carriers, the boron neutron capture compounds, some new mitosis-interactive agents, cell cycle modifiers, biological-response mpdifiers, oncogene inhibitors, drug-antibody conjugates, cancer cell suppression and destruction agents, antiangiogenesis and antimetastasis agents, apoptosis-promoting agents, and gene therapy and vaccines.

show abstract

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Section: Protein Kinase Inhibitorsmentioning

confidence: 99%

Section: Protein Kinase Inhibitorsmentioning

confidence: 99%

See 2 more Smart Citations

Critical appraisals of approaches for predictive designs in anticancer drugs

Gnewuch

Sosnovsky

2002

Cellular and Molecular Life Sciences (CMLS)

View full text Add to dashboard Cite

show abstract

“…The development of new antitumor drugs aimed at blocking the processes regulated by molecular markers is the most promising approach when the studied marker is directly involved in the regulation of cell proliferation and/or differentiation, as is the case with EGFR [4,5,7,17,83].…”

Section: Bulletin Of Experimental Biology and Medicine N O-i 1 1998mentioning

confidence: 99%

Epidermal growth factor receptors in breast cancer: from experiment to clinical practice

Кушлинский

Герштейн

1998

Bull Exp Biol Med

View full text Add to dashboard Cite

The role of auto-paracrine regulation of cell proliferation in breast cancer is analyzed. Experimental data indicate that the epidermal growth factor receptor is the key transmitter of mitogenic signals from the polypeptide growth factors and participates in the formation of sensitivity and/or resistance of breast cancer cells to steroid hormones. Data of representative clinical studies indicate that the expression of the epidermal growth factor receptor is prognostically unfavorable in breast cancer. Screening of patients with breast tumors for this receptor will detect the high-risk group at early stages of the disease. A scheme of the screening is proposed.Key Words: epidermal growth factor receptors; breast cancer; proliferation regulation; steroid hormone sensitivity; prognosis Epidermal growth factor receptor (EGFR) is a large transmembrane glycoprotein with a molecular weight of 170 kD. It is a product of an erb-c-erbB1 oncogene and belongs to so-called tyrosine kinases that are important regulators of cell proliferation and malignant transformation [17,32,46]. Transmembrane localization and need in relevant polypeptide ligand for realization of the kinase activity differs the receptor tyrosine kinases from the nonreceptor ones, which are also products of some important oncogenes, for example, v-src, v-abl, and bcr-abl.In addition to the epidermal growth factor (EGF), m-transforming growth factor (c~-TGR), Vaccinia virus growth factor, and the peptides amphiregulin, cripto and [3-cellulin binding heparin EGF-like factor act as specific EGFR ligands [12,23,53,75]. All these ligands are polypeptides consisting of about 40 amino acids with a molecular weight of about 6 kD. They are 24-40% homologous by primary structure and similar by spatial configuration due to con- Like molecules of all receptor tyrokinases, a EGRF molecule contains 3 major domains [17,75]: extracellular N-terminal glycosylated ligand-binding site constituting about 50% of the molecule (621 of 1173 amino acid residues) and ensuring specificity of the signal perception, transmembrane o~-spiral site consisting of only 23 hydrophobic amino acids, and intracellular tyrosine kinase domain (542 amino acids) similar in all receptor tyrokinases.Schematically, all main events in which EGFR is involved as a result of its reaction with the ligand are as follows [17,54,61,62,69,75]: immediately after the ligand binding, the receptor is dimerized, which leads to tyrosine kinase activation and autophosphorylation of tyrosine residues of the C-terminal domain and alteration of its conformation, thus promoting binding and phosphorylation of exogenous substrates and subsequent competitive inhibition of the receptor autophosphorylation. After autophos-0007-4888/98/0011-1073520.00 9Kluwer Academic/Plenum Publishers

show abstract

Comparative analysis of the sensitivity of endometrial cancer cells to epidermal growth factor and steroid hormones

Shatskaya

Костылева

et al. 1995

Cancer

View full text Add to dashboard Cite

Background. Epidermal growth factor (EGF) and EGF‐regulated processes play an important role in steroid signal transduction. Comparative analysis of EGF and steroid receptor expression and the sensitivity of early stages of proliferation induction, such as activation of phospholipid turnover to EGF and steroids, may provide a useful new approach to characterizing the sensitivity of endometrial cancer to hormone therapy. Methods. Progesterone (PR), estradiol (ER), and EGF receptor (EGFR) content was measured by radioligand competitive methods in surgically excised tumors from 26 patients with primary endometrial cancer. In short term cell cultures isolated from 11 of these tumors, the influence of a 10‐minute treatment with 10−8M EGF either alone or combined with 10−8M progesterone on 32P‐incorporation into phospholipids was studied. Phospholipids were fractionated by thin‐layer chromatography and were located by autoradiography, and quantification of the labeled compounds was made by densitometric scanning of the autoradiograms. Results. Epidermal growth factor receptor was found in 15 of 26 (58%) endometrial cancer samples. Eighty‐two percent of the tumors studied contained PR, and 81% contained ER. No significant correlations were revealed between EGFR and ER/PR status or concentration. Epidermal growth factor stimulated 32P‐incorporation by more than 120% of the control level in five of seven EGFR‐positive and in one of four EGFR‐negative endometrial cancer samples. An inverse relationship was revealed between EGFR content and the percentage of EGF‐induced stimulation of phospholipid turnover in endometrial cancer cells (r = −0.6; P = 0.15) and between EGFR content in EGFR‐positive samples and the extent of progesterone suppression of EGF‐induced turnover (r = −0.77; P = 0.04). Conclusions. Determination of EGF sensitivity on a receptor and a functional level may provide important additional information about the hormonal sensitivity of endometrial cancer.

show abstract

Signal transduction pathways: New targets in oncology

Cited by 5 publications

References 55 publications

Critical appraisals of approaches for predictive designs in anticancer drugs

Critical appraisals of approaches for predictive designs in anticancer drugs

Epidermal growth factor receptors in breast cancer: from experiment to clinical practice

Comparative analysis of the sensitivity of endometrial cancer cells to epidermal growth factor and steroid hormones

Contact Info

Product

Resources

About