In their ongoing quest to understand and treat children’s cancer, researchers are making great progress.  Following are some of the most significant findings from this past year.

Philadelphia Chromosome Positive ALL

The most common form of childhood cancer is Acute Lymphoblastic Leukemia (ALL) and within ALL there are a number of disease variations, one of which is called Philadelphia Chromosome Positive ALL (Ph+ ALL).  Until recently, the preferred treatment for Ph+ ALL was to perform a stem cell transplant after the patient had received 3-6 months of chemotherapy treatment.  Unfortunately, even with this aggressive therapy, cure rates were less than 50%and some of the children cured with stem cell transplant experienced serious long-term effects.

Now, new research performed by Children’s Oncology Group doctors has shown that treating children with Ph+ ALL using chemotherapy combined with a new drug called Imatinib can double cure rates.  Based on these findings, stem cell transplant is no longer automatically considered to be the best way to treat children with Ph+ ALL.

Neuroblastoma

Children's Oncology Group researchers announced that an analysis of more than 3,500 children with neuroblastoma showed that African American and Native American children were more likely to have high-risk, aggressive disease than Caucasian children. Both groups also had worse survival - - both overall and living disease-free without recurrence. As one next step, researchers are planning to analyze data from more than 3,600 African-American and Caucasian children with neuroblastoma to determine how pieces of DNA associated with resistance to chemotherapy drugs in the laboratory setting compare to results in patient outcomes.

Medulloblastoma

Researchers at Children’s Hospital Boston identified six subtypes of medulloblastoma with distinct molecular "fingerprints,” or biomarkers, that will improve doctors' ability to direct and individualize treatment. The Children’s Oncology Group will apply this information to patients in upcoming clinical trials and doing so will mark the first time biomarkers for medulloblastoma are used in the clinic setting.

Rhabdomyosarcoma

Researchers at Oregon Health & Science University, Doernbecher Children's Hospital have defined the cell-of-origin for rhabdomyosarcoma, or muscle cancer. Authors report that childhood and adult sarcomas are linked in their biology, mutations, and cells from which these tumors first start. These findings may lead to non-chemotherapy medicines that can inhibit "molecular targets" such as growth factor receptors, which would stop or eliminate the disease.

Approximately 350 children under the age of 15 are diagnosed with rhabdomyosarcoma each year.  CureSearch for Children’s Cancer is currently funding a number of COG trials examining the cellular structure of rhabdomyosarcoma in order to develop new medications.  One such trial is measuring the activity of various chemotherapies on 60 tissue samples to determine if inhibiting a specific protein improves responses to these medications.  The goal is that findings from these kinds of research studies in the laboratory lead to giving patients with rhabdomyosarcoma chemotherapy that is specifically targeted to those cells, thus improving response rates and helping to cure the disease.

Therapeutically Applicable Research to Generate Effective Treatments (TARGET)

Children’s Oncology Group (COG) and National Cancer Institute researchers partnered to perform a large scale genomic study on childhood Acute Lymphoblastic Leukemia (ALL) called TARGET (Therapeutically Applicable Research to Generate Effective Treatments).   In this study, researchers examined the genetic features of ALL patients from COG trials who were known to have a very high rate of treatment failure.  The goal was to find abnormalities in the leukemia cells that could help identify new, more targeted medications to treat children with ALL.

The researchers discovered that 5-10% of these ALL patients have previously unknown recurring mutations in genes called JAK, that play important roles in controlling growth and survival of ALL cells.  This led to development of a COG Phase I clinical trial, now underway, testing the safety and side effects of new medications called JAK inhibitors that can be taken by mouth.  COG researchers are already designing follow-up studies that will combine JAK inhibitors with standard chemotherapy drugs, with the goal of improving cure rates for this difficult to treat subset of childhood ALL.