Growth factor signalling in prostatic growth: significance in tumour development and therapeutic targeting.
The intricate balance maintained between cell growth and proliferation factors and apoptosis-inducing factors is fundamental to the regulation of prostate growth. Disruptions in this homeostasis often trigger the loss of apoptosis and the over-expression of factors promoting cell survival and proliferation, inevitably leading to tumorigenesis and cancer. Deregulation of prostate growth during prostate cancer development and progression is characterized by apoptotic evasion, uncontrolled proliferation, and increased invasive potential. Thus, in advanced stages of disease progression, surviving prostate tumour cells acquire the ability to migrate and invade heterotopic tissues, with the bone and lymph nodes being the most common sites for human prostate cancer metastasis. The challenges in the implementation of effective therapeutic strategies for the treatment of advanced metastatic prostate cancer reflect the multidimensional nature and functional significance of antiapoptotic pathways in the emergence of therapeutic resistance of prostate tumours. In this chapter, we discuss the current understanding of the molecular mechanisms governing growth factor signalling pathways with often overlapping functions that contribute to loss of apoptosis control and activation of cell proliferation towards aggressive prostate tumorigenic growth and metastatic behaviour. While a full understanding of the prosurvival characteristics of these growth factor pathways is still evolving, the impact that growth factors such a epidermal growth factor and transforming growth factor-beta can be recognized by the vigorous attempts at therapeutic targeting of their key signalling steps.
Reynolds
Arich Ryan
AR
Department of Surgery, University of Kentucky Medical Center, Lexington, KY 40536, USA. nkypr2@uky.edu
Kyprianou
Natasha
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I