Glioblastomas (GBMs) are among the most aggressive of all known human
tumors. The median survival times remain in the 12- to 15-month range despite aggressive surgery, radiation, and
chemotherapy. Through molecular and genetic profiling efforts, underlying mechanisms of resistance to these
therapies are becoming better understood. The present standard of care has been shaped by the recently reported phase III study by the European Organisation for Research and Treatment of
Cancer and the National Cancer Institute of Canada, which found that the addition of
temozolomide (TMZ) to
radiation therapy significantly improved outcome compared with radiation alone. However, careful examination of these data reveals that not all GBM patients benefited from the addition of TMZ to
radiation therapy. A companion correlative study found that GBM patients with
tumors with MGMT promoter methylation appeared to derive the greatest benefit from the addition of TMZ to
radiation therapy. Although this finding is provocative, it should be kept in mind that this study was performed retrospectively and that prospective validation is required before MGMT methylation can be used for clinical stratification purposes. However, this study does show promise for the tailoring of future treatments according to the molecular and genetic profiles of an individual's
tumor rather than using the "one-glove-fits-all" approach that is currently being followed. As more effective "smart drugs" are developed, molecular and genetic profiling will assume even greater importance in this regard.