The incidence and severity of toxicity, tumor response to treatment and survival serve as primary endpoints for defining the dose (Phase I) and assessing the activity (Phase II) and efficacy (Phase III) of anticancer drugs. Researchers at the Center for Childhood Cancer Research (CCCR), including Frank M. Balis, MD, are working to identify biomarkers that will sensitively detect and accurately measure the intensity of critical organ toxicities before long-term damage occurs to serve as surrogate endpoints for Phase I trials.

The standard chemotherapy regimen used to treat osteosarcoma, the most common type of bone cancer in children and adolescents, includes two drugs that can damage the kidneys. An ongoing clinical trial in the CCCR is studying new approaches to lessen or circumvent the kidney damage caused by these drugs.  The primary endpoint of this trial is a panel of acute kidney injury biomarkers measured in the urine 24 hours after the drugs are administered. These biomarkers are more sensitive than standard clinical tests of kidney function, and can provide a rapid assessment of the impact of the new preventive measures.

In addition, biomarkers that reflect tumor burden are being developed to measure response to anticancer drugs and potentially serve as a surrogate endpoint that could predict for survival on Phase III trials. Predictive biomarkers would have the potential to substantially expedite clinical drug development.

CCCR investigators are focused on identifying and validating serum tumor biomarkers for neuroblastoma and osteosarcoma. If these biomarkers, which are shed from tumor cells into the circulation, accurately reflect the burden of viable tumor, they could potentially be used to measure response to treatment and estimate the likelihood that a patient will survive their cancer.

Tumor biomarkers also serve as diagnostic tools and for assessing prognosis at the time of initial presentation.