Incorporating molecular tools into clinical trials and treatment for gliomas?

PURPOSE OF REVIEW

Knowledge of the molecular biology of gliomas may improve therapy. This review highlights several recent studies on this topic.

RECENT FINDINGS

Gliomas are the most common primary brain tumors in adults, and remain refractory to therapy despite decades of work. Discoveries in the last several years have led to a better understanding of glioma biology. These include the importance of O6-methylguanine-DNA-methyltransferase (MGMT) in glioblastoma sensitivity to the DNA alkylating chemotherapy temozolomide. In addition, coexpression of phosphatase tensin homolog on chromosome ten (PTEN) and a mutant variant of the epidermal growth factor receptor (EGFRvIII) appears to predict sensitivity of recurrent glioblastomas to EGFR inhibitors. Finally, loss of heterozygosity for chromosomes 1p and 19q correlates with both response to therapy and improved prognosis for patients with oligodendrogliomas. The best way to incorporate these findings into office practice, however, remains unclear, especially in the absence of effective alternatives to currently available treatments. While subdividing gliomas molecularly may allow tailoring of therapy to individual patients based on individual tumor biology, a superior strategy may be to identify common molecular abnormalities that are targets of more universally applicable therapies.

SUMMARY

It remains unclear how best to integrate recent discoveries regarding glioma molecular biology into clinical practice.