289Clinical implementation of these results is expected to greatly improve routine
glioma diagnostics and will enable a patient specifi c therapeutic approach. In order
to develop a routine-diagnostic test for chemosensitivity prediction that is widely
applicable and cost-effective, an established multiplex ligation dependent probe
amplifi cation (MLPA) assay for OT diagnostics will be revamped by adding novel
biomarkers that are identifi ed by a combined array-approach. MLPA analysis will
be performed on archival, paraffi n embedded tissue of a set from clinically well-
documented gliomas, and marker patterns will be identifi ed that correlate with clini-
cal outcome. Protocols will be established that are able to distinguish chemosensitive
and chemoresistant tumors, and implementation of these protocols in routine diag-
nosis will enable tailored chemotherapy for individual glioma patients, thereby
avoiding unnecessary harmful side effects and improving their quality of life.
Personalized Therapy of Neuroblastomas
Neuroblastoma usually arises in the tissues of the adrenal glands but is also seen in
the nerve tissues of the neck, chest, abdomen and pelvis. It responds to chemother-
apy with topotecan, which interacts with a critical enzyme in the body called topoi-
somerase. This enzyme helps DNA unwind so it can replicate, and topotecan inhibits
its function, leading to cell death. However, fi nding the optimum dosage for treating
neuroblastoma can be tricky.
A technique called pharmacokinetic-based (PK-based) dosing improves the
response to treatment by monitoring and fi ne tuning topotecan drug levels. PK-based
dosing reduces variability in the amount of topotecan in the body, leading to
improvements in response and ultimately to improvement of the odds of survival.
The aim is to get the right dosage of topotecan for a good antitumor effect and to
minimize toxicity. In a prospective phase II trial, topotecan was administered with
PK-guidance on a protracted schedule to achieve targeted systemic exposure and
was found to be active against neuroblastoma (Santana et al. 2005 ). The aim of the
initial treatment with the drug is to quickly reduce the size of the tumor that must be
surgically removed. Reducing tumor size with topotecan and surgery also reduces
the risk that the cancer will develop resistance to standard chemotherapy drugs that
are administered afterward. The children with PK-guided drug administration did
exceedingly well and tolerated the therapy with few ill effects. PK-based topotecan
dosing is also being used for the brain tumor medulloblastoma and the eye cancer
retinoblastoma. The scientists are now working on a method where they could tell
pediatric oncologists that they could adjust the topotecan dosage according to
patient characteristics to get a better antitumor effect and not even need to check
blood levels. This would be a personalized approach to treatment.
Children with high-risk neuroblastoma have a poor clinical outcome. Vaccination
with antigen-loaded dendritic cells (DCs) is being investigated for these children.
Loading of DCs with apoptotic neuroblastoma cells or transfection with tumor
mRNA represents promising strategies for development of individualized cancer
vaccines/cancer gene therapy in treatment of neuroblastoma.
Personalized Management of Cancers of Various Organs