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glioma stem-like cells, including CD133 and nestin. Finally, a multigene predictor
of outcome in GBM was identifi ed, which is applicable to routinely processed FFPE
samples. The profi le has potential clinical application both for optimization of ther-
apy in GBM and for the identifi cation of novel therapies targeting tumors refractory
to standard therapy. The assay is commercially available as DecisionDx-GBM
(Castle Biosciences Inc).
IDH1 Genotype and Survival After Surgical Resection of GBM Survival ben-
efi t associated with surgical resection differs based on IDH1 genotype in
GBM. Therapeutic benefi t from maximal surgical resection, including both enhanc-
ing and non-enhancing tumor, may contribute to the better prognosis observed in
the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant
astrocytoma may be considered based on IDH1 status (Beiko et al. 2014 ).
Personalized Chemotherapy of Brain Tumors
Although ~26 % of patients treated with temozolomide survive >2 years, it is diffi -
cult to predict who would respond to therapy. A number of tests are used to deter-
mine the responsiveness of GBM to chemotherapy.
Gene Promoter Methylation Testing The O6-methylguanine-DNA methyltrans-
ferase (MGMT) gene is located at chromosome 10q26 and codes for a DNA repair
enzyme that counteracts the effects of alkylating chemotherapy. In GBM patients
the MGMT gene is usually inactivated due to aberrant methylation of its promoter
region. Assessment of the MGMT promoter methylation status is clinically relevant
as a bi0marker of response to alkylating chemotherapy and prolonged survival of
GBM patients. MGMT promoter methylation testing has also been used as a bio-
marker for patient selection in clinical trials, e.g., CENTRIC trial that was specifi -
cally focused on patients with MGMT promoter-methylated GBM. MGMT
promoter methylation is a favorable prognostic biomarker independent of the type
of therapy, i.e., radio- or chemotherapy (Riemenschneider et al. 2010 ). Several
methods are being used to assess MGMT promoter methylation in clinical samples.
MGMT gene test (MDxHealth Inc) is used as a Laboratory Developed Test or as
Investigational Use Only tool in the assessment of patients participating in clinical
trials. Future clinical trials will determine, the degree to which MGMT promoter
methylation is predictive or prognostic for each subtype of glioma, and if testing
should be used in practice for the management of patients with GBM.
Molecular Determinants of Response to EGFR Inhibitors EGFR is amplifi ed,
overexpressed, or mutated in 50 % of GBM cases, but only 10–20 % of patients
have a response to EGFR kinase inhibitors. In patients with recurrent GBM, coex-
pression of EGFRvIII and PTEN by tumor cells is associated with responsiveness to
EGFR kinase inhibitors. One inherent resistance mechanism that faces use of EGFR
inhibitors in GBM is the coactivation of multiple receptor tyrosine kinases, which
generates redundancy in activation of phosphoinositide-3′-kinase (PI3K) signaling.
10 Personalized Therapy of Cancer