Smart drugs in prostate cancer.
OBJECTIVE
Growth signaling is instrumental in tumor development. Insight into signaling pathways by molecular and cellular biology has changed the development of new anticancer agents. Outside the field of urology specifically targeted drugs such as imatinib mesylate and gefitinib showed impressive anticancer activity in chronic myeloid leukemia and non-small cell lung cancer, respectively.


METHODS
Literature search of PubMed documented publications and abstracts from meetings.


RESULTS
Preclinical data in prostate cancer shows upregulation of a wide variety of growth factors and their receptors such as PDGF, EGF, IGF, FGF, and VEGF suggesting efficacy of agents targeting these pathways. Here the preclinical evidence and first clinical data on the use of growth signal targeting in prostate cancer is reviewed. Although some anticancer efficacy of signal transduction inhibition monotherapy was reported, combination with chemotherapy and radiotherapy seemed most promising in prostate cancer.


CONCLUSIONS
So-called smart drugs are small molecules targeted at specific growth signaling pathways. These new drugs will dominate clinical trials in the years to come either as single-drug modality, but more likely as combination treatment.
van der Poel
H G
HG
Department Urology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. h.vd.poel@nki.nl
D019883:Alkyl and Aryl Transferases / Q000502:physiology; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000502:physiology; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology; D051231:Farnesyltranstransferase; D005346:Fibroblast Growth Factors / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology
D019883:Alkyl and Aryl Transferases; D000726:Androgen Antagonists; D000728:Androgens; D016232:Endothelins; D051231:Farnesyltranstransferase; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D010982:Platelet-Derived Growth Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D042442:Vascular Endothelial Growth Factors