Current Pharmaceutical Design - Volume 23, Issue 1, 2017

Background: Productivity in drug R continues seeing significant attrition in clinical stage testing. Approval of new molecular entities proceeds with slow pace specifically when it comes to chronic, age-related diseases, calling for new conceptual approaches, methodological implementation and organizational adoption in drug development. Methods: Detailed phenotyping of disease presentation together with comprehensive repr Read More

Background: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro- RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, Read More

Background: Hedgehog signaling pathway is a developmental pathway mostly inactive in adult tissues, with the exception of stem cells. It is often found upregulated in various tumors, and associated with cancer stem cell maintenance. Methods: This review focuses on different aspects of Hedgehog activation in tumors, with special emphasis on ovarian tumors and their treatment. Results: Mutations in pathway component Read More

Background: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have e Read More

Background: Notch is a multifaceted protein that plays a fundamental role in fetal development and tissue homeostasis by directing many cellular functions, including cell growth and differentiation, cell fate determination and regulation of stem cells maintenance. The Notch family consists of four receptors (Notch 1-4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human tissues. Given the crucial contrib Read More

Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells differentiation, with the main consequence of peripheral cytopenias and inc Read More

Background: Hepatocellular carcinoma (HCC) represents the most common malignant liver tumor in humans, which incidence and mortality have increased in Europe and United States in the last years. Most patients are diagnosed at an advanced stage, when it is not amenable to curative therapies, so there is an urgent need for new, more effective therapeutic tools and strategies. The molecular mechanisms of hepatocari Read More

Background: Deletion of phenylalanine 508 is the most frequent mutation causing cystic fibrosis. It causes multiple defects: 1) misfolding of the protein causing retention at the ER (processing defect); 2) reduced channel activity (gating defect); 3) reduced plasma membrane residency time due to increased internalization rate and defective recycling. Methods: Druggability of F508del-CFTR was demonstrated by several studi Read More

Background: The field of bile acid research has become tremendously active. Bile acids have been shown to act as signaling molecules that are involved in many metabolic processes, but their role in carcinogenesis is also emerging. Methods: The aim of this review was to summarize the present knowledge in the innovative field of bile acids pharmacology, to reveal the novel mechanisms of their action, particularly focusin Read More