Growth factors involved in prostate carcinogenesis.
Prostate cancer is the most common non-skin cancer affecting men in United States and the second leading cause of death after lung cancer. The clinical course of patients after given diagnosis of prostate cancer is highly variable and the underlying reasons for such variability remain elusive. To better understand the pathophysiology of prostate cancer, there has been a push to elucidate the molecular mechanisms that mediate the development and progression of prostate cancer. Recent literature has pointed that a complex interplay between various cytokines, growth factors, and androgen receptors regulate the growth and functions of the prostate gland. Amongst the currently implicated anomalous pathways involved in prostate oncogenesis, the IGF-IGFBP axis has been demonstrated to play a very important role, although the precise molecular events regulated by IGF remain to be elucidated. The tumor promoting functions of VEGF has been defined in tumor angiogenesis and currently remains the central focus of anti-angiogenesis therapy in prostate cancer. Another key cytokine, TGF-beta has tumor-suppressor functions in normal prostate gland, but its pleiotropic functions in prostate cancer are influenced by the hormonal state of the disease. In partnership with other deregulated growth factor signaling, the TGF-beta cascade has also been implicated in the spread of prostate cancer. Lastly, members of the EGFR family, particularly the HER2 receptor, have also been recognized as crucial elements of aberrant signal transduction pathways, which induce activation of downstream signaling, involved in cellular proliferation, cell survival, and angiogenesis. The abnormal function of a number of growth factors in prostate cancer biology explains the heterogeneity of its histologic grade, mode of presentation and disease prognosis. At the same time, continued research in this field allows for the potential development of drug therapies against a diverse pool of cancer causing targets.
Kambhampati
Suman
S
Cancer Research Unit, Kansas City VA Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, USA. Suman.Kambhampati@med.va.gov
Ray
Gibanananda
G
Sengupta
Krishanu
K
Reddy
Venkataprasanth P
VP
Banerjee
Sushanta K
SK
Van Veldhuizen
Peter J
PJ
D015197:Carcinogenicity Tests; D066246:ErbB Receptors / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D006133:Growth Substances; D007328:Insulin; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors