Current Drug Targets - Volume 12, Issue 8, 2011

Regardless of the extended use of anticancer agents even in multiple drug regimens, chemotherapy failure habitually occurs even in the most sensitive malignancies (i.e., breast cancer). This is mainly the consequence of: i) an extensive biodistribution and rapid plasma clearance which lead to ineffective drug concentrations into the tumor tissue; and, ii) multi-drug resistances exhibited by cancer cells. Drug delivery strategies Read More

Due to a very poor specificity, many chemotherapy agents generate a low antitumor effect and important severe side effects. Poly(D,L-lactide-co-glycolide) (PLGA)-based nanomedicines are under investigation to assure a very efficient anticancer activity in chemotherapy. In this work, we analyze the major applications of this FDA-approved biodegradable polymer in the formulation of nanomedicines against cancer. Despit Read More

Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; Read More

Nanotechnology provides researchers with new tools for cancer treatment. Biodegradable polymeric nanoparticles, as an advanced drug delivery system, have promising applications in cancer treatment. Poly(ε- caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymers are biodegradable and amphiphilic, and show potential application in drug delivery. In recent years, PCL/PEG copolymeric nanoparticles, as a potential nanoplat Read More

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse Read More

The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO2). Char Read More

Ras-related small GTP-binding proteins (also commonly referred to as small GTPases) comprise a large group of highly conserved signaling proteins with more than 100 mammalian family members. Many of these proteins are components of signaling pathways that link extracellular signals via transmembrane receptors to cytoplasmic or nuclear responses. Based on structure, sequence and function, the Ras superfamily can be Read More

The Rab family of GTPases contains over 60 genes in the human genome and contributes to regulation of intracellular membrane trafficking along endocytic and exocytic pathways as well as specialized pathways in specific cell types. It has become increasingly clear that disruption of the intracellular membrane trafficking system at different stages can cause various diseases. In the past decade, altered expression levels a Read More

Rho GTPases (Ras homologous family) comprise the largest subfamily cluster of the Ras-homology superfamily. Rho GTPases exist in inactive GDP and active GTP forms. The active forms of the Rho family members bind with numerous effector proteins that are crucial for various biological processes. Accumulating evidence exemplifies the importance of Rho effector proteins in various steps of cancer progression. Here, we Read More

The establishment of neural connectivity implicates tight regulation of the intracellular signaling pathways mediated by axon guidance molecules. The Rho family of small GTPases, in particular Rho, Rac, and Cdc42, are important regulators of the cytoskeleton in neuronal cells acting, downstream of most, if not all, guidance cue receptors. Furthermore, recent studies using in vivo knockout mouse models provide new e Read More

Several mechanisms function in the endocytic regulation of the Wnt/β-catenin signaling pathway to promote or interrupt the progression of critical cellular processes during embryonic development or disease progression. Endocytosis was initially associated with the formation of a morphogen gradient of Wnt/β-catenin signaling, but current studies have documented its role in defining signal intensity and propagation. Although t Read More

mTOR exists in two distinct complexes. mTOR complex 1 (mTORC1) is potently inhibited by the immunosupressive macrolide rapamycin; whereas, mTORC2 is insensitive to this drug. These mTOR complexes play an integral role in the regulation of many cellular processes including protein synthesis, autophagy, lipid synthesis, mitochondrial metabolism/biogenesis, and cell cycle. Both mTOR complexes are important for mai Read More