Molecular markers and determinants of prostate cancer metastasis

Abstract

Although intensely studied, the molecular and biochemical determinants of prostate cancer development and progression remain ill-de®ned. Moreover, current markers and methodologies cannot distinguish between a tumor that will remain indolent and not impinge on patient survival, versus a tumor with aggressive traits culminating in metastatic spread and death. Once prostate cancer is con®rmed the most signi®cant threat to a patient's survival and quality of life involves tumor metastasis. Radical surgery notwithstanding, prostate cancer accounts for 10% of all cancer-related deaths primarily arising through development of metastasis. Metastasis markers demonstrating an acceptable level of reliability are an obvious necessity if disproportionate and costly treatment is to be avoided and a reasonably accurate determination of clinical prognosis and measure of successful response to treatment is to be made. Therapeutic strategies that speci®cally inhibit metastatic spread are not presently possible and may not become available in the immediate future. This is because, while localized tumorigenesis has been relatively amenable to detection, analysis and treatment, metastasis remains a relatively unde®ned, complex and underexplored area of prostate cancer research. New ®ndings in the ®eld such subclasses of genes called metastasis suppressors and cancer progression suppressors, have opened up exciting avenues of investigation. We review current methodological approaches, model experimental systems and genes presently known or having potential involvement in human prostate cancer metastasis.

Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

“…In the initial stages, prostate cancer is dependent on androgens for growth and can be suppressed using androgen deprivation therapy. However, tumor growth eventually recur due to a transition from an androgen-dependent to an androgen-independent state, leading to a highly metastatic disease that eventually kills the patient (41). In addition to androgens, growth factors, including pleiotrophin, have been shown to play a key role in the development and progression of the disease (11,(42)(43).…”

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

“…[29][30][31][32][33] Moreover, as prostate cancer is a relatively slow-growing disease, it may be necessary to use repeated gene therapy approaches, with single or multiple genes, over the lifespan of the patient. 3 In these contexts, the use of replication defective Ads for administering therapeutic and/or cytotoxic genes in prostate tumor cells represents promising treatment options.…”

“…3 In these contexts, the use of replication defective Ads for administering therapeutic and/or cytotoxic genes in prostate tumor cells represents promising treatment options. [32][33] Gene therapy, through either enforced expression or suppression of target gene overexpression, represents a potentially viable approach for the treatment of malignant and benign disorders. Ad is the best characterized of all viral-based delivery approaches, and Ad.5 is the most frequently used vector for therapeutic purposes.…”

CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer

“…Hormonal therapy (i.e., androgen deprivation) initially induces antitumor response in more than 90% of patients. However, it eventually fails and the PCa progresses to an androgen-insensitive stage that is essentially incurable (2).…”