REVIEWSNew approaches to primary brain tumor treatmentSathornsumetee, Sitha b; Rich, Jeremy N.a b cAuthor Information Departments of aMedicine bSurgery cNeurobiology, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA Correspondence to J. N. Rich, Departments of Medicine, Surgery and Neurobiology, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, DUMC 2900, Durham, NC 27710, USA. Tel: +1 919 681 1693; fax: +1 919 684 6514; e-mail: [email protected] Sponsorship: This work was supported in part by funds from the Childhood Brain Tumor Foundation, Accelerate Brain Cancer Cure and the Pediatric Brain Tumor Foundation of the United States (J.N.R.). This work was also supported by NIH grants NS047409, NS054276 and 1 P50 CA108786 (J.N.R.). J.N.R. is a Damon Runyon–Lilly Clinical Investigator supported by the Damon Runyon Cancer Research Foundation and a Sidney Kimmel Cancer Foundation Scholar. Note: Due to the breadth of the area under review, it was not possible to include many excellent studies conducted by our colleagues in neuro-oncology in the space allotted. We regret the omissions. Received 17 April 2006 Accepted 5 June 2006 Anti-Cancer Drugs: October 2006 - Volume 17 - Issue 9 - p 1003-1016 doi: 10.1097/01.cad.0000231473.00030.1f Buy Metrics Abstract Primary brain tumors represent over 100 different tumor types with widely divergent biologies and clinical outcomes, but these neoplasms frequently pose similar challenges to neuro-oncologists. Malignant gliomas are the most common type of primary intrinsic brain tumor in adults and remain extremely lethal. Current standard-of-care therapies for these cancers include surgery, radiation and palliative cytotoxics, which have significant side-effects and limited efficacy. Advances in our understanding of the molecular underpinnings of cancer have led to targeted molecular therapies that may permit improvement in therapeutic efficacy and reduced toxicity; these therapies, however, still face many challenges. Signal transduction pathways that are inappropriately regulated in brain cancers include growth factors and their receptors (e.g. epidermal growth factor receptor, vascular endothelial growth factor receptor and platelet-derived growth factor receptor), which regulate cellular interactions with the microenvironment and intracellular oncogenic pathways. Low-molecular-weight inhibitors have been developed to target many kinases and may have advantages in terms of delivery. Monoclonal antibodies may have greater specificity, but face delivery restrictions. Preferential tumor delivery of chemotherapies, conjugated toxins and radioisotopes has been achieved through convection-enhanced delivery, intratumoral implants and intra-arterial infusion. Despite these advances, few molecularly targeted therapies have demonstrated significant antineoplastic activity for a broad range of patients, possibly due to tumor and patient heterogeneity. Improved functional neuropathology and imaging may permit identification of patient subgroups for which clinical responses may be enriched. It is probable, however, that targeted therapies will be most effective in combination either with one another or with cytotoxic therapies. In this study, we review the current state of new therapies for malignant gliomas. © 2006 Lippincott Williams & Wilkins, Inc.