Novel Therapies in Glioblastoma

Conventional treatment of glioblastoma has advanced only incrementally in the last 30 years and still yields poor outcomes. The current strategy of surgery, radiation, and chemotherapy has increased median survival to approximately 15 months. With the advent of molecular biology and consequent improved understanding of basic tumor biology, targeted therapies have become cornerstones for cancer treatment. Many pathways (RTKs, PI3K/AKT/mTOR, angiogenesis, etc.) have been identified in GBM as playing major roles in tumorigenesis, treatment resistance, or natural history of disease. Despite the growing understanding of the complex networks regulating GBM tumors, many targeted therapies have fallen short of expectations. In this paper, we will discuss novel therapies and the successes and failures that have occurred. One clear message is that monotherapies yield minor results, likely due to functionally redundant pathways. A better understanding of underlying tumor biology may yield insights into optimal targeting strategies which could improve the overall therapeutic ratio of conventional treatments

Parallel pathways of repression and antirepression governing the transition to stationary phase in Bacillus subtilis

The AbrB protein of the spore-forming bacterium Bacillus subtilis is a repressor of numerous genes that are switched on during the transition from the exponential to the stationary phase of growth. The gene for AbrB is under the negative control of the master regulator for entry into sporulation, Spo0A∼P. It has generally been assumed that derepression of genes under the negative control of AbrB is achieved by Spo0A∼P-mediated repression of abrB followed by rapid degradation of the AbrB protein. Here, we report that AbrB levels do decrease during the transition to stationary phase, but that this decrease is not the entire basis by which AbrB-controlled genes are derepressed. Instead, AbrB is inactivated by the product of a uncharacterized gene, abbA (formerly ykzF), whose transcription is switched on by Spo0A∼P. The abbA gene encodes an antirepressor that binds to AbrB and prevents it from binding to DNA. Combining our results with previous findings, we conclude that Spo0A∼P sets in motion two parallel pathways of repression and antirepression to trigger the expression of diverse categories of genes during the transition to stationary phase