Search

The current standard of care for malignant gliomas consists of surgery, radiotherapy and conventional (DNA-damaging) chemotherapies. These treatments are relatively nonspecific and may be applied to all glioma subtypes. Developments in cancer medicine, however, now offer the opportunity to direct therapies to specific molecular pathways involved in tumorigenesis. This offers the potential to tailor treatments to tumor subtypes--perhaps with greater efficacy and less toxicity. Many of the so-called targeted therapies are under investigation in the treatment of malignant glioma. In this review, we will focus on the use of agents that affect signal transduction. In particular, we will review the potential role for inhibitors of: tyrosine kinases, targets of rapamycin, farnesyl transferase and histone deacetylase. Inhibitors of angiogenesis will also be discussed. Some 'targeted' therapies are less specific than others, working on more than one pathway or receptor, thus complex interactions are possible.

RimasV Lukas1, Adrienne Boire2, M Kelly Nicholas1,2 1Department of Neurology; 2Department of Medicine, University of Chicago, Chicago, IL, USAAbstract: Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In addition, we will discuss strategies that target the extracellular matrix in which these cells reside as well as angiogenesis, a process emerging as central to tumor development and growth. Finally, we will briefly touch on the role of neural stem cells as both potential targets as well as delivery vectors for other therapies. Interdependence between these varied pathways, both in maintaining health and in causing disease, is clear. Thus, attempts to easily classify some targeted therapies are problematic.Keywords: glioma, EGFR, mTOR, HDAC, Ras, angiogenesis