Contemporary management of high-risk localized prostate cancer.
ABSTRACT The management of high-risk, localized prostate cancer remains a formidable challenge despite significant technical advances in surgery and radiation therapy. Treatment outcomes of radiation therapy are improved by the addition of adjuvant androgen deprivation therapy, whereas, with surgery, oncologic results are enhanced with either postoperative radiation therapy or androgen deprivation therapy in select cases. In high-risk prostate cancer, disease recurrence after primary therapy may occur at either distant or local sites. Ongoing studies are in the process of evaluating systemic therapy for the eradication of local and micrometastatic disease. Neoadjuvant therapies offer the opportunity to maximize local control as a path to improved outcomes and critically evaluate agent effectiveness in the target tissue. The treatment for high-risk localized prostate cancer is in evolution. It is likely that the development of effective strategies based on understanding prostate tumor biology will lead to significant advances in the treatment of this disease.
- SourceAvailable from: Declan G MurphyBJU International 03/2011; 107(6):1009; author reply 1009-10. DOI:10.1111/j.1464-410X.2011.10145_1.x · 3.13 Impact Factor
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ABSTRACT: Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.Cell cycle (Georgetown, Tex.) 04/2011; 10(7):1121-31. DOI:10.4161/cc.10.7.15180 · 5.01 Impact Factor
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ABSTRACT: Prostatic adenocarcinomas are reliant on androgen receptor (AR) activity for survival and progression. Therefore, first-line therapeutic intervention for disseminated disease entails the use of AR-directed therapeutics, achieved through androgen deprivation and direct AR antagonists. While initially effective, recurrent, 'castrate-resistant' prostate cancers arise, for which there is no durable means of treatment. An abundance of clinical study and preclinical modeling has led to the revelation that restored AR activity is a major driver of therapeutic failure and castrate-resistant prostate cancer development. The mechanisms underpinning AR reactivation have been identified, providing the foundation for a new era of drug discovery and rapid translation into the clinic. As will be reviewed in this article, these creative new ways of suppressing AR show early promise.Expert Review of Endocrinology & Metabolism 05/2011; 6(3):483-493. DOI:10.1586/eem.11.33