Targeting of EGFR tyrosine kinase by ZD1839 ("Iressa") in androgen-responsive prostate cancer in vitro.
EGFR, highly expressed in a variety of human malignancies, is correlated with poor tumour differentiation, high tumour growth and metastatic rate. EGF and several other ligands, such as transforming growth factor-alpha, amphiregulin, heparin-binding EGF, and betacellulin, activate Ras/Raf mitogen-activated protein kinases (MAPKs) and phosphatidyl inositol 3'-kinase (PI3K)/Akt signalling pathways. Therefore, EGFR can regulate multiple processes, i.e., gene expression, cellular proliferation, angiogenesis, and inhibition of apoptosis, which contribute to the development of malignancy. In this review, we discuss the inhibition of EGFR by the specific tyrosine kinase inhibitor Iressa (ZD1839) focusing on its effects in prostate cancer.
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, Sezione di Biochimica Cellulare, Università di Perugia, via del Giochetto, 06123 Perugia, Italy.
Ilaria
I
Bellezza
Sergio
S
Bracarda
Claudia
C
Caserta
Alba
A
Minelli
D000728:Androgens / Q000502:physiology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015398:Signal Transduction
D000728:Androgens; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib