Current Pharmaceutical Design - Volume 19, Issue 4, 2013

Cancer remains a fundamental burden to public health despite substantial efforts aimed at developing effective chemotherapeutics and significant advances in chemotherapeutic regimens. The major challenge in anti-cancer drug design is to selectively target cancer cells with high specificity. Research into treating malignancies by targeting altered metabolism in cancer cells is supported by computational approaches, which c Read More

Research on cancer epigenetics has flourished in the last decade. Nevertheless growing evidence point on the importance to understand the mechanisms by which epigenetic changes regulate the genesis and progression of cancer growth. Several epigenetic targets have been discovered and are currently under validation for new anticancer therapies. Drug discovery approaches aiming to target these epigenetic enzymes Read More

Sirtuins are a family of NAD+-dependent enzymes that was proposed to control organismal life span about a decade ago. While such role of sirtuins is now debated, mounting evidence involves these enzymes in numerous physiological processes and disease conditions, including metabolism, nutritional behavior, circadian rhythm, but also inflammation and cancer. SIRT1, SIRT2, SIRT3, SIRT6, and SIRT7 have all been linked to c Read More

Post-translational modifications of cellular proteins by mono- or poly-ADP-ribosylation are associated with numerous cellular processes. ADP-ribosylation reactions are important in the nucleus, and in mitochondrial activity, stress response signaling, intracellular trafficking, and cell senescence and apoptosis decisions. These reversible reactions add ADP-ribose to target proteins via specific enzymes to form the ADP- Read More

Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, Read More

Glycogen synthase kinase 3 (GSK-3) is a ubiquitous serine/threonine protein kinase participating in numerous pathways. Very important among them are cancer-related pathways, such as Wnt pathway and nuclear factor κB pathway. The recent findings concerning possible applicability of GSK-3 inhibitors as anticancer agents are summarized in this review, and controversies in the data are highlighted. The most actual con Read More

The last quarter of a century has witnessed remarkable progress in the understanding of phosphoinositide 3-kinases (PI3K) signalling and their involvement in different diseases such as cancer, diabetes and inflammation. Nevertheless, many questions remain open and among these the role of genetic and epigenetic regulation of PI3K isoforms is one of the most prominent. Emerging evidence Indicates that levels of isoforms Read More

Fibroblast growth factor receptors (FGFRs) play an important role in embryonic development, angiogenesis, wound healing, cell proliferation and differentiation. The fibroblast growth factor receptor (FGFR) isoforms have been under intense scrutiny for effective anticancer drug candidates. The fibroblast growth factor (FGF) and its receptor (FGFR) provide another pathway that seems critical to monitoring angiogenesis. Rece Read More

Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this revi Read More

Cell type specification, transcription factor binding site selection and transcriptional regulation are specific processes that require a fine regulation that cannot be simply explained by the mere DNA sequence. Similarly, genome stability, damage response as well as genomic imprints and X-chromosome inactivation are all processes that involve an epigenetic level of regulation. This includes the activity of several enzymes th Read More

Multiple Myeloma (MM) is a common hematologic malignancy of plasma cells representing an excellent model of epigenomics dysregulation in human disease. Importantly, these findings, in addition to providing a better understanding of the underlying molecular changes leading to this malignance, furnish the basis for an innovative therapeutic approach. Histone deacetylase inhibitors (HDACIs), including Vorinostat and Read More

The deregulation of microRNAs expression and activity is frequently observed in a wide variety of human pathologies including cancer. Accordingly, growing evidence indicates that the targeting of microRNAs biogenesis and pathways is emerging as a central tool for the development of novel RNA-based drugs and therapies to defeat diseases in humans. In this review we describe the various strategies that can be used to targ Read More

Colorectal cancer (CRC) is a major health problem causing significant morbidity and mortality. During the last decade, results from different studies indicate that the pathogenetic mechanisms of CRC encompass tumour microenvironment, emphasizing a tight correlation with aging, inflammation, nutrition, gut microbiome composition and epigenetic modifications. Aging is one of the most important risk factors for the development Read More

Data mining, a part of the Knowledge Discovery in Databases process (KDD), is the process of extracting patterns from large data sets by combining methods from statistics and artificial intelligence with database management. Analyses of epigenetic data have evolved towards genome-wide and high-throughput approaches, thus generating great amounts of data for which data mining is essential. Part of these Read More

Cancer metabolism is currently re-evaluated by the research community with the aim to investigate possible opportunities for the development of targeted therapies. Firstly discovered by Warburg et al. in the beginning of the last century, it is now a widely accepted hypothesis that cancer cells possess a severely deregulated form of glycolysis also under aerobic conditions. Accompanied by a deregulated glycolysis is an increasi Read More