Pharmacological targeting of the integrated protein kinase B, phosphatase and tensin homolog deleted on chromosome 10, and transforming growth factor-beta pathways in prostate cancer.
Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is much desired. Central to this goal is the development of novel targeted pharmacological interventions. To develop these treatment strategies, an understanding of the integration of cellular pathways involved in both tumorigenesis and tumor suppression is crucial. Of further interest are the events elicited by drug treatments that exploit the underlying molecular pathology in cancer. This review briefly describes the evidence that suggests integration of three established pathways: the tumorigenic phosphoinositide 3-kinase/protein kinase B (AKT) pathway, the tumor suppressive phosphatase and tensin homolog deleted on chromosome 10 pathway, and the tumor suppressive transforming growth factor-beta pathway. More importantly, we discuss novel pharmaceutical agents that target key points of integration in these three pathways. These new therapeutic strategies include the use of agents that target iron to inhibit proliferation via multiple mechanisms and suppression of AKT by cytosolic phospholipase A(2)-alpha inhibitors.
Assinder
Stephen J
SJ
Discipline of Physiology , School of Medical Sciences, Bosch Institute Prostate Cancer Focus Group, University of Sydney, Sydney, New South Wales, Australia.
Dong
Qihan
Q
Mangs
Helena
H
Richardson
Des R
DR
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human