Steroids are a highly effective component of therapy for acute lymphoblastic leukemia (ALL).  However, patients whose leukemia does not respond to steroid therapy have high risk for relapse and poor prognosis.  New understanding of and therapies for steroid resistance are critical to progress in ALL therapy.  Cells respond to steroids via the glucocorticoid receptor (GR), which binds DNA and cooperates with the SWI/SNF complex to modify gene expression.  The SWI/SNF complex modulates packaging of DNA, thereby controlling access of other proteins necessary for gene expression.  Subunits of t

Neuroblastoma is the most frequent extra-cranial solid tumor in children, accounting for almost 10% of all childhood cancers and close to 15% of childhood cancer deaths. Amplification of the MYCN gene occurs in up to 40% of neuroblastomas, which results in very high levels of MYCN protein and is a marker of very poor prognosis. Current treatment strategies for MYCN amplified tumors are ineffective and in desperate need of new therapeutic avenues. Successful disruption of MYCN function in neuroblastoma would be an exciting therapeutic breakthrough and would save lives.

Myelodysplastic syndrome (MDS) is caused by the abnormal development of blood cells. Currently, the symptoms of MDS can be treated, but the disease itself remains incurable. About 50% of MDS-cases develop into deadly leukemia. The main reason that MDS is difficult to treat is that it is not a single disease, but consists of many subtypes with different symptoms and different underlying causes. To unravel MDS we need to exploit animal models, such as the zebrafish, that can realistically capture the complex disease and are accessible to experimental analysis in living animals.

More children die from acute lymphoblastic leukemia (ALL) than any other cancer. About one-third of patients develop serious side effects (such as another cancer) as a consequence of treatment. We need to better define the molecular origins of ALL to develop new medicines that are more effective and less toxic. Many ALLs arise from T-cells. About one-third of patients with T-cell ALL carry a cancer gene called TLX1. Mice in which scientists have artificially removed the TLX1 gene are healthy. Thus, TLX1 is an attractive drug target. Blocking TLX1 should spare normal healthy tissue.

Rhabdomyosarcoma is the most common soft tissue cancer in childhood. Despite rigorous clinical trials, the survival for children with high-risk rhabdomyosarcoma has not changed for three decades. The children that do survive often suffer from life-long disfigurements as a result of the aggressive treatment. Thus, there is a tremendous need for the development of novel treatments of this disease. Rhabdomyosarcoma resembles developing skeletal muscle and has been speculated to originate from genetically compromised skeletal muscle progenitors.