Current Pharmaceutical Design - Volume 18, Issue 19, 2012

Over the last decades, the issue of developing novel target-based strategies for medical treatment of human neoplasias has become more and more relevant; in this context, the wider availability of more sophisticated molecular biology techniques has fuelled great enthusiasm in the possibility to clarify in-depth the molecular features of pathways critical for cancer biology, and to design more individualizes therapies. Read More

Members of epidermal growth factor receptor (EGFR) or ErbB receptor family play a critical role in a wide range of human cancers. In the past decade, there has been a remarkable progress in developing ErbB targeted therapeutics. However, a substantial portion of patients has non-responsive disease or subsequently shows evidence of tumour relapse following initial success with anti-ErbB agents. Improved insights i Read More

Tumour angiogenesis (formation of new blood vessels supporting tumour growth and metastasis) is a result of complex interactions between the tumour and the surrounding microenvironment. Targeting tumours with anti-angiogenic therapy remains an exciting area of preclinical and clinical studies. Although many significant advances have been achieved and the clinical use of anti-angiogenic drugs is now well recognized in Read More

In the last decades, the active research in the field of tumor angiogenesis has led to the development of a class of agents providing an effective inhibition of neo-vessel formation through the blockade of VEGF related pathways. More recently, the identification of other factors involved in tumor angiogenesis, such as platelet-derived growth factor, fibroblast growth factor and Angiopoietins has emphasized the need to dev Read More

Gynecologic cancer is a major burden in both developed and developing countries. Almost a half million deaths from gynecologic cancer are reported each year. Understanding the molecular biology of cancer is a principle resource leading to the identification of new potential therapeutic targets, which may be parlayed into novel therapeutic options in gynecologic cancer. Focal adhesion kinase (FAK) is a non-receptor tyros Read More

To assure their growth advantage cancer cells require the appropriation of key pathways, such as those controlled by G-protein coupled receptor (GPCR), that influence cell growth, migration, and death, as well as the expansion of vascular networks. Accumulating molecular and in vivo evidences demonstrate that the activation of the endothelin-1 (ET-1) axis elicites pleiotropic effects on tumour cells and on the tumour Read More

While it is well documented that the mitogenic actions of estrogens are critical in the development and progression of human breast and some gynecologic cancers, only latest data demonstrate a crucial involvement of estrogen-signaling in the carcinogenesis of non-classical estrogen target tissues, as colon, prostate, lung, skin, and brain. Only recently it has also been found out that the biological effects of estrogens a Read More

FMS-like tyrosine kinase-3 (FLT3) is a tyrosine kinase receptor involved in the survival and expansion of hematopoietic stem progenitors. A constitutively activated, mutated form of FLT3, is expressed in approximately 30% of de novo acute myeloid leukemia (AML) and about 6% of acute lymphoblastic leukemia (ALL) cases. Since mutant FLT3 has emerged as an attractive therapeutic target, there are several FLT3 inhibitor Read More

Background: The mammalian target of rapamycin (mTOR) is a protein kinase involved in the phosphatidylinositol 3-Kinase (PI3K)/AKT signalling pathway with a central role in the control of cell growth, survival and angiogenesis. Multiple and frequent dysregulations of this pathway in human tumors make it a central target in the development of new anticancer treatments. Objective: To review the most significant data on mT Read More

Tubulin is the target of some of the most widely used and time-honored anticancer tubulin-binding agents (TBAs). The clinical usefulness of many TBAs has been held back as a result of tumor cell drug-resistance. The elucidation of the three-dimensional structure of αβ-tubulin dimer has provided an opportunity for rational drug design aimed at generating compounds that will target tubulin in therapeutically more efficaci Read More

Among the drugs targeting microtubule functions by interfering with tubulin subunits, epothilones represent a class of anticancer agents which recently entered clinical development. Although epothilones share mechanisms of action similar to taxanes, they have non-overlapping mechanisms of resistance; in particular, while overexpression of class III β-tubulin plays a major role in taxane resistance, epothilones di Read More

The microtubule (MT) represents a highly validated target for therapy. Insights into the complex nature of the dynamic microtubule physiology will provide the basis for developing novel microtubule targeting agents with enhanced efficacy and minimised toxicity. In this article, with an emphasis on translational applications, we have summarised relevant aspects of tubulin physiology in the context of developing MT binding agents Read More

Gemcitabine is one of the most widely used pyrimidine analogues, with a well-established role as a first- and second-line treatment of several types of tumors. Several preclinical and clinical studies have been done to obtain information on molecular determinants of gemcitabine activity and metabolism, in order to predict whether this drug will be effective and safe for the individual patient. Among these molecular determina Read More

Chemoradiotherapy is an important treatment paradigm in oncology and is part of the curative treatment for many solid cancers, such as lung, pancreatic and cervical cancers. One of the main goals in oncology research is to develop approaches that can improve the efficacy of chemoradiotherapy while minimizing treatment toxicity. A new and exciting approach is to incorporate advances in nanomedicine into c Read More

Cancer stem cells (CSCs) were identified in human leukemias in landmark studies of John Dick and his colleagues. Subsequently, similar cancer stem-like cells were identified in solid tumors of the breast, colon, brain and other sites. CSCs have distinct markers and are highly tumorigenic compared to other subsets. They can differentiate into all the cell phenotypes of the parental tumor. Other key features include activatio Read More