Current Pharmaceutical Design - Volume 17, Issue 23, 2011

Fighting against cancer has variable results, depending on the tumour type. Major improvements have been achieved during the past three decades for breast, prostate and colorectal cancer. In many cases, patients with those diagnoses can actually be cured, or at second best, live in hopes that their cancer may have become a manageable disease, accompanied by a decent quality of life. The story is different with hig Read More

The discovery of discrete functional components in cancer systems advocates a paradigm shift in therapeutic design towards the targeted destruction of critical cellular constituents that fuel tumorigenic potential. In astrocytomas, malignant growth can be propagated and sustained by glioma stem cells (GSCs) endowed with highly efficient clonogenic and tumor initiation capacities. Given their disproportionate oncogenic Read More

Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). The significance of CSCs is underscored by their resistance to cytotoxi Read More

The tumor environment is critical for tumor maintenance and progression. Integrins are a large family of cell surface receptors mediating the interaction of tumor cells with their microenvironment and play important roles in glioma biology, including migration, invasion, angiogenesis and tumor stem cell anchorage. Here, we review preclinical and clinical data on integrin inhibition in malignant gliomas. Various pharmacolo Read More

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The treatment options for patients diagnosed with GBM are limited and the current median survival is 14-16 months following diagnosis. Genetic mutations have been identified that act as drivers of GBM growth and these should be considered as a basis for identifying novel therapeutic strategies. AKT is a downstream serine/threonine kin Read More

Cancer metabolism has gained considerable interest, since significant studies have indicated a close relationship between the activation of various oncogenes and alterations of cellular metabolism. Furthermore, several lines of evidence have shown that metabolic imaging can significantly impact malignant glioma patient management and monitoring of tumor response to therapy. In this context, mitochondria play a central Read More

The endoplasmic reticulum (ER) stress response represents a cellular “yin-yang” process, where low to moderate activity is cell protective and supports chemoresistance (yang), but where more severe conditions will aggravate these mechanisms to the point where they abandon their protective efforts and instead turn on a cell death program (yin). Because tumor cells frequently experience chronic stress conditions (d Read More

Glioblastoma (GBM) is a deadly tumor, which in spite of surgery and radio/chemotherapy frequently undergoes relapses related to the infiltration of the normal parenchyma and to resistance to cytotoxic and radiation therapy. Immunotherapy may represent a promising approach, which may complement existing therapies with the aim of eliminating residual tumor cells, through their selective targeting by immune effector cell Read More

High-grade gliomas, including glioblastoma, are among the most malignant and treatment-refractory human neoplasms. The tumors show high levels of resistance to conventional therapies (i.e. surgery, irradiation, and chemotherapy), and despite treatment advances patient outcome remains poor. New therapeutic options are needed. An especially interesting idea is the rational development of new therapies targeting Read More