New frontiers in the treatment of malignant glioma.
Despite many technologic advances in neuroimaging, neurosurgery, and radiation therapy, there has been little improvement in survival for patients with malignant glioma. Given the failure of traditional treatment approaches to significantly improve survival in patients with malignant gliomas, research in this field has focused on gaining a better understanding of the molecular pathogenesis of gliomas with the goal of identifying novel drug targets and therapeutic strategies. The influence of molecular genetics on response and survival has been best shown in oligodendrogliomas. The hallmarks of low-grade and anaplastic oligodendrogliomas are their exquisite sensitivity to chemotherapy and favorable prognosis, which are correlated with loss of heterozygosity of chromosomes 1p and 19q. Together, loss of heterozygosity of 1p and 19q appears to confer responsiveness to chemotherapy and to correlate with improved survival. In contrast, deletion of the CDKN2A gene is correlated with poor response to chemotherapy and poor survival, and loss of heterozygosity of chromosome 10q is associated with shorter progression-free and overall survival compared with intact 10q. A variety of other molecular genetic abnormalities have been recognized in gliomas, and these genetic changes are not only important prognostic factors, but also offer new therapeutic targets. With the increased use of improved surgical and radiotherapy techniques and targeted biologic therapy over the next 20 years, many patients with malignant gliomas may be cured or their disease may be controlled for the long term. Molecular profiling of patients using gene chip technology will likely become commonplace, and many patients will receive a tailored treatment regimen based on the unique genetic profile of their tumor.
Macdonald
David R
DR
London Regional Cancer Centre, 790 Commissioners Road East, London, Ontario N6A 4L6 Canada.
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001691:Biological Therapy; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005910:Glioma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D006801:Humans; D018579:Patient Selection; D015996:Survival Rate
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor