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Abstract: Globally Prostate Cancer is the second most commonly diagnosed and sixth leading cause of Cancer mortalities in men worldwide but currently there is no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastasis are the main causes of treatment resistance and mortality in Prostate Cancer patients. Although several advances have been made to control yet there is an urgent need to investigate the mechanisms and pathways for chemoresistance and prostate cancer (PCa) metastasis. Cancer stem cells (CSCs), a sub-population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer relapse but also contribute substantially to chemoresistance. Contributing to the role of CSCs are the miRNAs which are known key regulators of the posttranscriptional regulation of genes involved in a wide array of biological processes including tumorigenesis. The altered expressions of miRNAs have been associated with not only with tumor development but also with invasion, angiogenesis, drug resistance, and metastasis. Thus identification of signature miRNA associated with EMT and CSCs would provide a novel therapeutic strategy for the improvement of current treatment thus leading to increase in patient’s survival. Keywords: Cancer stem cells, Epithelial to Mesenchymal Transition, Metastasis, MicroRNA.Download Full Article |
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Abstract: Prostate cancer is the second most common lethal cancer in men worldwide. Despite the fact that the prognosis for patients with localized disease is good, many patients succumb to metastatic disease with the development of resistance to hormone treatments. This is normally termed castration-resistant prostate cancer (CRPC). The development of metastatic, castration-resistant prostate cancer has been associated with epithelial-to-mesenchymal transition (EMT), a process where cancer cells acquire a more mesenchymal phenotype with enhanced migratory potential, invasiveness and elevated resistance to apoptosis. The main event in EMT is the repression of epithelial markers such as E-cadherin and upregulation of mesenchymal markers such as N-cadherin, vimentin and fibronectin. The insulin-like growth factor (IGF) signalling axis is essential for normal development and maintenance of tissues, including that of the prostate, and dysregulation of this pathway contributes to prostate cancer progression and malignant transformation. It is becoming increasingly clear that one of the ways in which the IGF axis impacts upon cancer progression is through promoting EMT. This review will explore the role of EMT in prostate cancer progression with a specific focus on the involvement of the IGF axis and its downstream signalling pathways in regulating EMT in prostate cancer. Keywords: Epithelial-to-mesenchymal transition, insulin-like growth factor family, prostate cancer progression, lifestyle factors.Download Full Article |
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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 |
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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 |
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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 |