Current Drug Targets - Volume 17, Issue 15, 2016

Endothelial to mesenchymal transition (EndMT) is a poorly understood phenomenon that results in normal endothelial cells acquiring a mesenchymal phenotype. EndMT has been observed in a number of pathological conditions, from cancer to fibrosis to cardiovascular disease and the process itself may play an important mechanistic role in the development of these disease states.

Antiangiogenic resistance is a major problem in cancer therapeutics. Preclinical research has identified several compensatory proangiogenic pathways that arise upon vascular endothelial growth factor inhibition, several of which have led to the development of novel drugs. However, the combination of two or more targeted agents in the angiogenesis system is hampered by toxicity, as the system is involved in normal phy Read More

The mechanisms of tumor growth and progression involve the activation of different processes such as neovascularization and angiogenesis. These processes involve tumoral cells and stromal cells. Hence, inhibiting angiogenesis affects tumor growth and proliferation in patients with different types of cancer. Nevertheless, tumoral cells and stromal components are responsible for the resistance to antiangiogenic therapies. The Read More

One proposed mechanism through which antiangiogenics exert their effect in epithelial malignancies is by improving the status of the aberrant vascular network and secondarily facilitating the delivery of concurrently administrated cytotoxic agents. During this process, known as vascular normalization, the oxygenation of the tumor is usually improved. Many mechanisms of resistance have been proposed to evade the acti Read More

Drug resistance remains an ongoing challenge for the majority of patients treated with inhibitors of the vascular endothelial growth factor (VEGF) pathway, a key regulator of tumor angiogenesis. Preclinical models have played a significant role in identifying multiple complex mechanisms of antiangiogenic treatment failure. Yet questions remain about the optimal methodology to study resistance that may assist in making clin Read More

Background: Sporadic data are available about pazopanib use in patients with metastatic renal cell carcinoma (mRCC) undergoing dialysis and no systematic review has been previously performed about this issue. Objective: The objective of the present mini-review is to provide an overview of clinical outcomes of pazopanib in this population, in order to support the clinical oncologist for the treatment choice and management. Read More

Sox (SRY-related HMG-box) family genes are important regulators of cell development, homeostasis, and regeneration. Deregulation of certain members of the Sox gene family has been implicated in a number of human malignancies, including in sarcoma. Accumulating evidence suggests that Sox genes play crucial roles in sarcoma cell pathogenesis, growth, and proliferation. Here, we review the biological relevance of So Read More

Poor absorption, short half-life and resistance development are some of the major factors responsible for reduced drug efficacy. Lipophilic prodrugs can offer certain advantages to overcome these challenges. Chemical derivatization of hydrophilic agents with lipophilic pro-moieties can significantly elevate drug diffusion across absorptive membranes. Moreover, the desired linkage (ester vs. amide) may be selected to im Read More

The chemical modifications of polysaccharides involve the use of chemical methods to modify some special structures or functional groups of polysaccharides on the main chains or side chains. The chemical methods include sulfation, phosphorylation, acetylation, carboxymethylation etc. Therefore, spatial structures, and physical and chemical properties of polysaccharides change, which enhance the biological activities of Read More

Cirrhosis is a diffuse pathophysiological state of the liver considered to be the final stage of various liver injuries, characterized by chronic necroinflammatory and fibrogenetic processes, with subsequent conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment and collapse of the liver tissue. Alcoholic liver disease and chronic infections due t Read More

Gastric and gastro-esophageal cancers (GC/GEJ) appear as the second cancer-related death worldwide. Diagnosis is made at an advanced stage offering a curative attempt in less than 50% of cases. Despite the improvements of the systemic cytotoxic chemotherapy regimens, the prognosis of patients with metastatic GC/GEJ cancer remains poor. Recent insights in biochemical pathways have permitted to identify potential tar Read More