The End of the Beginning: Circulating Tumor Cells As a Biomarker in Castration-Resistant Prostate Cancer

Journal of Clinical Oncology (Impact Factor: 18.43). 03/2014; 32(11). DOI: 10.1200/JCO.2013.54.7307
Source: PubMed
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    ABSTRACT: Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge.
    Oncotarget 09/2014; 5(17):7217-59. DOI:10.18632/oncotarget.2406 · 6.36 Impact Factor

  • Indian journal of medical and paediatric oncology 10/2014; 35(4):237-8. DOI:10.4103/0971-5851.144962
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    ABSTRACT: Results of clinical trials have demonstrated that circulating tumour cells (CTCs) are frequently detected in patients with urothelial tumours. The monitoring of CTCs has the potential to improve therapeutic management at an early stage and also to identify patients with increased risk of tumour progression or recurrence before the onset of clinically detected metastasis. In this study, we report a new effectively simplified methodology for a separation and in vitro culturing of viable CTCs from peripheral blood. We include patients diagnosed with 3 types of urothelial tumours (prostate cancer, urinary bladder cancer, and kidney cancer). A size-based separation method for viable CTC - enrichment from unclothed peripheral blood has been introduced (MetaCell, Ostrava, Czech Republic). The enriched CTCs fraction was cultured directly on the separation membrane, or transferred from the membrane and cultured on any plastic surface or a microscopic slide. We report a successful application of a CTCs isolation procedure in patients with urothelial cancers. The CTCs captured on the membrane are enriched with a remarkable proliferation potential. This has enabled us to set up in vitro cell cultures from the viable CTCs unaffected by any fixation buffers, antibodies or lysing solutions. Next, the CTCs were cultured in vitro for a minimum of 10 to 14 days to enable further downstream analysis (e.g., immunohistochemistry). We demonstrated an efficient CTCs capture platform, based on a cell size separation principle. Furthermore, we report an ability to culture the enriched cells - a critical requirement for post-isolation cellular analysis.
    Canadian Urological Association journal = Journal de l'Association des urologues du Canada 10/2014; 8(9-10):E715-E720. DOI:10.5489/cuaj.1978 · 1.92 Impact Factor
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