Molecularly targeted therapy for malignant glioma

• Published in: Cancer 2007-07, Vol.110 (1), p.13-24
• Main Authors: Sathornsumetee, Sith, Reardon, David A., Desjardins, Annick, Quinn, Jennifer A., Vredenburgh, James J., Rich, Jeremy N.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain Neoplasms - pathology; Brain Neoplasms - physiopathology; Brain Neoplasms - therapy; Combined Modality Therapy; glioblastoma; glioma; Glioma - pathology; Glioma - physiopathology; Glioma - therapy; Humans; Intercellular Signaling Peptides and Proteins - physiology; kinase inhibitor; Medical sciences; Models, Biological; Neurology; Receptors, Growth Factor - physiology; Signal Transduction - physiology; targeted therapy; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22741

Malignant gliomas are relatively uncommon but lethal cancers. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant gliomas has remained dismal. Understanding the molecular pathogenesis of glioma may lead to a rational development of new therapies. Despite the genetic heterogeneity of malignant gliomas, common aberrations in the signaling elements of the growth and survival pathways are found. New treatments have emerged to target molecules in these signaling pathways with the goal to increase specific efficacy and minimize toxicity. Monoclonal antibodies and low molecular‐weight kinase inhibitors are the most common classes of agents in targeted cancer treatment. Most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit in unselected malignant glioma patient populations. Several mechanisms of treatment failure have been demonstrated. In response, multitargeted kinase inhibitors and combinations of single‐targeted kinase inhibitors have been developed to overcome therapeutic resistance. In addition, multimodality combinations of targeted agents with radiation, chemotherapy, or immunotherapy/vaccines may enhance treatment efficacy. Future development of these agents will require advances in discovery and validation of new molecular targets, improvement of therapeutic delivery, and identification of correlative biomarkers. Novel clinical trial designs and endpoints may increase the efficiency of new drug evaluation. In this review, the authors discussed the current understanding of molecular pathogenesis and the development of molecularly targeted therapies in malignant glioma. Cancer 2007. © 2007 American Cancer Society. Recent advances in neuro‐oncology research have elucidated several molecular abnormalities underlying the pathogenesis of malignant glioma. In this review, the authors discuss the current understanding of molecular aberrations and the rational development of molecularly targeted therapies in malignant glioma.