Diffuse Intrinsic Pontine Glioma: A Therapeutic Challenge

Diffuse intrinsic pontine glioma (DIPG) is a tumor of the brainstem, specifically in the pons, accounting for 10–20% of all of central nervous system (CNS) tumors in children. Unfortunately, DIPG is the leading cause of death in children with CNS cancers. Clinical interventions trying to effectively treat children with DIPG have failed despite 40 years of clinical trials. The critical location of these tumors eliminates extensive surgical resection as an option. Radiation therapy (RT) is the standard of care, and although it improves the clinical symptoms of most patients, the results are temporary, with tumor progression typically occurring months post radiation. Given the dismal prognosis associated with this disease and the challenge to find chemotherapeutic agents, especially molecularly targeted drugs that improve the survival of the patients, there is a strong incentive to move new treatments forward into clinical trials. The more effective treatment would potentially involve combinatory therapeutic regimens with new epigenetic drugs that can offer synergistic benefits and potentially increase therapeutic efficacy. The increasing knowledge of genomic, epigenomic, and proteomic characteristics of DIPG is opening doors to new therapeutic avenues and provides hope and promise for this devastating childhood cancer

Snake Venom Disintegrins and Cell Migration

Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion