Current Drug Targets - Volume 18, Issue 4, 2017

The use of imatinib, second and third generation ABL tyrosine kinase inhibitors (TKI) (i.e. dasatinib, nilotinib, bosutinib and ponatinib) made CML a clinically manageable and, in a small percentage of cases, a cured disease. TKI therapy also turned CML blastic transformation into a rare event; however, disease progression still occurs in those patients who are refractory, not compliant with TKI therapy or develop resistance to Read More

The complete eradication of Chronic Myeloid Leukemia is still challenging even in the era of highly selective and potent BCR-ABL tyrosine kinase inhibitors (TKIs). The ‘Achilles heel’ of TKI-based CML therapy is the inability of TKI to effectively target CML stem cells. Several pathways have been described to induce TKI insensitiveness in quiescent CML stem cells. In this review, we will describe the BCR-ABL/HAUSP/PML/PTEN netwo Read More

Chronic Myelogenous Leukemia (CML)-initiating cells (CICs) express the hybrid oncoprotein BCR-ABL at the highest levels compared to their differentiated progeny but fail to expand at the same rate as downstream leukemic myeloid cells. Moreover, the primitive stem cell clone that originates the indolent CML chronic phase (CP) remains almost invariant as the disease evolves to a fatal blast crisis (BC). Compared to t Read More

The introduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) has revolutionised disease outcome. However, despite this, progression to blast phase disease is high in those that do not achieve complete cytogenetic and major molecular response on standard therapy. As well as BCR-ABL-dependent mechanisms, disease persistence has been shown to play a key role. Disease persistence suggests that, des Read More

Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial and life-threatening chronic infections in cystic fibrosis patients. This pathogen is wellknown for its ability to attach to surfaces of indwelling medical devices to form biofilms, which consist of a regular array of extracellular polymers. Tenaciously bound to the surface of devices and inherently resilient to antibiotic treatment, Read More

Akt kinase is a serine threonine kinase that exists in three isoforms, located in different chromosomes and has distinct sites of expression which orchestrates diverse cellular processes required for normal functioning of the cell. Though, these Akt isoforms have some overlapping actions, but they also have specific roles and interestingly, sometimes they even perform contrasting functions. There are various alterations such a Read More

Patients who underwent solid organ transplantation frequently suffer from different skin diseases, as consequence of the immunosuppressive treatment. Specific cutaneous side effects such as acne, hypertricosis or other pilosebaceous unit disorders, gingival hyperplasia, purpura or teleangiectasies are commonly associated to immunosuppressive medications. The majority of these conditions are benign, but the aest Read More

Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ ind Read More

Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally identified as a crucial regulator of actin cytoskeleton. Recent studies have defined new functions of ROCK as a critical component of diverse signaling pathways in neurons. In addition, inhibition of ROCK causes several biological events such as increase of neurite outgrowth, axonal regeneration, and activation of prosurvival Akt. Thus, it has attracted sci Read More

MicroRNAs (miRNAs) are small conserved noncoding RNAs which function as posttranscriptional regulators of gene expression. Studies over the last 20 years have revealed the essential functions of miRNAs in regulating cardiovascular biology (such as cardiovascular cell differentiation, growth, proliferation and apoptosis) and crucial roles in controlling cardiovascular disease (CVD), indicating the potential of these small molecule Read More

Mammalian sirtuins (SIRT1-7) are NAD+-dependent deacetylases, which play an important role in aging and in a wide range of cellular functions. SIRT1, the best-characterized member of the family, acts as a sensor of the redox state and triggers in the cell the appropriate defense response. A large body of evidence has showed that SIRT1 induces both cellular and systemic protective effects in the cardiovascular system by pr Read More

The definition of personalized treatments in tumor disease could lead to an improvement of the therapeutic success rate. Therefore, biomarkers are urgently required in order to select the patients that could benefit from adjuvant therapies in the initial phase of the disease and to better define and treat the clinical/therapeutic subgroups in the advanced pathological phases. Disregulation of cytokine physiological network Read More