The importance of c-Kit and PDGF receptors as potential targets for molecular therapy in breast cancer.
Molecular therapies target key functional molecules in order to halter viable operation of cancer cells. Receptor tyrosine kinases (RTKs) constitute attractive targets, as quite often their abnormal signaling has been associated with tumor development and growth. Overexpression of growth factor receptors, including IGF, EGF, TGF-alpha, SCF and PDGF receptors, has been associated with poor prognosis in breast cancer. Therefore, a number of RTKs are already targets for novel designed drugs, which involve tyrosine kinase inhibitors and monoclonal antibodies. Despite the fact that c-Kit and PDGF-R have been effective targets in a number of cancers, the experimental results in breast have not yet clarified their importance. The expression and function of c-Kit in breast cancer is a quite controversial subject. Several studies propose that the loss of c-Kit expression has been associated with tumor progress, whereas other reports indicate not only its expression but also the implication of c-Kit in breast cancer. On the other hand, the expression of PDGF-R in breast cancer is not in question. A number of inhibitors against tyrosine kinases are currently in trials as to demonstrate their importance in breast cancer treatment. Imatinib (STI571), which is a selective tyrosine kinase inhibitor and particularly of c-Kit and PDGF-R, exhibited encouraging results in respect to its inhibitory effect in cell growth and invasion potential in a panel of human breast cancer cell lines. In this review, the importance of RTKs in human cancer and of c-Kit and PDGF-R as molecular targets in breast cancer treatment, in the view of their expression profiles and the in vitro effects of STI571 is discussed.
Roussidis
A E
AE
Laboratory of Biochemistry, Department of Chemistry, University of Patras, 261 10 Patras, Greece.
Theocharis
A D
AD
Tzanakakis
G N
GN
Karamanos
N K
NK
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor