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Abstract : Neuroendocrine Differentiation and Epithelial to Mesenchymal Transition in Prostate Cancer: cAMP-Dependent Signaling as a Therapeutic Target
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Abstract: Prostate cancer exhibits both epithelial to mesenchymal transition and neuroendocrine differentiation. The major barrier to targeting epithelial to mesenchymal transition is that it is heavily involved with normal biology, such as wound repair. In prostate cancer, cAMP can trigger both neuroendocrine differentiation and epithelial to mesenchymal transition in a Snail-dependent manner We will review inhibition of cAMP-signaling as a target for drug development with the goal of simultaneously blocking both neuroendocrine differentiation and epithelial to mesenchymal transition in a tissue and tumor selective manner. Keywords: Androgen-independent prostate cancer, protein kinase A, adenylyl cyclase, Snail, cyclic nucleotide phosphodiesterase, heterotrimeric G protein.Download Full Article |
Abstract : Extracellular HSP90 in Cancer Invasion and Metastasis: From Translational Research to Clinical Prospects
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Abstract: During the last decade, the extracellular molecular chaperone HSP90 (eHSP90) has been identified as a critical effector in cancer cell invasion and metastasis by virtue of its interaction with a diverse cohort of molecules that serve as key nodal points in oncogenic pathways. Thus eHSP90 has most recently emerged as a novel target in cancer therapeutics, subsequently becoming the focus of several drug development efforts. This review highlights recent studies on the mechanisms through which eHSP90 exhibits its tumor cell invasion action. It also presents latest efforts to translate this cumulative knowledge into clinical practice to disable eHSP90-driven metastasis. Keywords: Cancer therapeutics, wound healing, cell impermeable antibodies, signal transduction, pro-motility factors, extracellular.Download Full Article |
Abstract : Erlotinib as Second-Line Therapy for Patients with Advanced Non-Small-Cell Lung Cancer and Wild-Type EGFR Tumors
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Abstract: Aim: The objective of the study was to determine the efficacy and safety of erlotinib in second-line therapy for patients with advanced non-small-cell lung carcinoma (NSCLC) and wild-type tumors, measuring progression-free survival (PFS), the response rate, and overall survival (OS). Material and Methods: This retrospective, observational, and multicenter study involved 47 patients diagnosed with NSCLC and wild-type epidermal growth factor receptor(EGFR) who received erlotinib as second-line therapy in four Spanish hospitals. Primary and secondary endpoints included the determination of the efficacy (by measuring progression-free survival, PFS, the response rate, and overall survival, OS) and safety profile of erlotinib. Results: The median PFS was 2.33 months (95% CI, 0.4–10.9). No differences in PFS were found regarding sex, age, smoking habits, ECOG performance status, and tumor histology. The median OS was 4.00 months (95% CI, 1.18–6.82). Four patients developed grade 3–4 non-hematological toxicities, including asthenia, cutaneous toxicity, and renal failure. One patient developed grade 3–4 thrombocytopenia. Conclusion: Our study corroborates the modest but clear benefit of second-line agents, including erlotinib, for the treatment of advanced NSCLC, and supports their administration in patients with wild-type EGFR. Further prospective studies involving large number of patients are required to corroborate such results. Keywords: Non-small-cell lung carcinoma, EGFR, wild-type, erlotinib, second-line.Download Full Article |
Abstract : The Management of Lower Urinary Tract Obstruction in Patients with Advanced Prostate Cancer
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Abstract: Objectives: To determine the optimal time to wait for urination ability restoration after urethral catheterization and anti – androgen treatment, in cases of acute urinary retention and advanced prostate cancer. Methods: We enrolled 26 patients with histologically confirmed prostate cancer after transrectal ultrasound guided biopsy of the prostate and CT or MRI proven advanced stages (T3-T4). We evaluated the dynamic changes of the following factors; IPSS, QoL, Vmax, residual urine, serum concentration of PSA at the following periods; before hormonal treatment, 1, 3 and 6 months after hormonal treatment. Results: How long we have to wait after urethral catheter insertion and hormonal treatment for voiding ability restoration? Our data analyses revealed the answer to this question. The dynamic changes of all the parameters (IPSS, QoL, Vmax, PSA) we studied disclosed interesting regularity. The consequent comparative analyses of parameters showed statistically significant changes only 1 month after anti – androgen treatment. These changes indicate that the prostate cancerous process is significantly suppressed within 1 month after hormonal treatment and there is no point to wait more than 1 month. Conclusion: Analyzing our data we obtained versatile evidence, that in advanced prostate cancer and acute urinary retention cases the optimal time to wait for sufficient voiding is 1 month period after permanent catheter insertion and anti – androgen treatment. Keywords: Non-small-cell lung carcinoma, EGFR, wild-type, erlotinib, second-line.Download Full Article |
