Current Cancer Drug Targets - Volume 11, Issue 1, 2011

Almost 50 years ago, David Hungerford and Peter Nowell first described the Philadelphia chromosome as characteristic cytogenetic abnormality in Chronic Myeloid Leukemia (CML, reviewed in [1]). In the following decades, the advent of molecular biology allowed the exact characterization of the molecular pathogenesis of the disease, which served as basic knowledge for subsequent development of tyrosine kinase inhibitors ( Read More

CML is characterized by the presence of the Philadelphia chromosome, which is the product of a reciprocal translocation between chromosomes 9 and 22 that results in the formation of BCR-ABL1. Apart from its diagnostic importance in CML patients BCR-ABL1 it is a potent oncogene. The natural evolution of CML is to progress into accelerated phase and blast crisis after a rather indolent chronic phase. Clinical experience s Read More

Clonal hematopoiesis triggered by somatic mutations plays a central role in the pathogenesis of Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPNs). After the discovery of JAK2 and MPL mutations, continual technological advances have led to the identification of increasing numbers of genetic defects in MPN patients, most of them chromosomal aberrations such as deletions and a Read More

The elucidation of the triggering molecular mechanism of chronic myeloid leukemia gave rise to the development of imatinib, a tyrosine kinase inhibitor and a prototype of target-oriented drugs. Imatinib led to impressing response and survival rates and now represents the standard therapy of CML. However, a significant proportion of patients do not tolerate or fail to respond to imatinib treatment. Alternative therapies can b Read More

Since William Dameshek has described the concept of “myeloproliferative disorders (MPD)” by identifying common clinical characteristics (i.e. hemorrhage, thrombosis and leukemic transformation) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), the advent of molecular biology has provided substantial molecular insight into the pathobiology of myeloproliferative neoplasia ( Read More

The concept of leukemic stem cells (LSC) is increasingly employed to explain the biology of various myeloid neoplasms and to screen for essential targets, with the hope to improve drug therapy through elimination of disease initiating cells. Although the stem cell hypothesis may apply to all neoplasms, leukemia-initiating cells have so far only been characterized in some detail in advanced acute (AML) and chronic myeloid leu Read More

The four major entities that form the group of myeloproliferative neoplasms (MPN) are BCR-ABL positive chronic myeloid leukaemia (CML), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET) and polycythemia vera (PV). All four are clonal diseases of the haematopoietic stem or precursor cell, they are of a chronic nature and potentially aggravate to myelofibrosis or transform into acute leukaemia. Sever Read More

The topic of this review covers a very important branch of cancer research, cancer vaccination. The growing knowledge in tumor immunology has evolved rapidly, starting from unspecific generic stimulation of the immune system to more specific approaches based on the availability of tumor antigens. The review covers molecular and cell biology, and pharmaceutical technology of cancer vaccines. Particularly, it is aimed at hi Read More

Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials are rare. The role of therapeutic vaccines in advanced cancer patients, if any, would be to decrease the ra Read More

Purpose: Oncolytic viral therapy is a newly developed modality to treat tumors. Many clinical trials worldwide have examined the efficacy of locally injected oncolytic viruses. However, systemic intravascular injections are limited by the humoral immune response, which dramatically decreases the level of infection. To overcome this limitation, we encapsulated the oncolytic virus in liposomes. Methods: The infectious properties o Read More

Background and aim: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-ba Read More