Department of Pediatric Oncology

The Department of Pediatric Oncology is committed to promoting laboratory research, translational investigation, and clinical studies to better understand and treat childhood cancers.

A focus on translational research

Stuart Orkin, MD, Chair 

Research across the continuum from laboratory research to clinical trials is most likely to contribute to the development of novel therapeutics. The Department's research focus accordingly spans cancer biology, leukemia research, sarcomas, neurobiology, and chemical biology. Through Dana-Farber/Children's Hospital Cancer Center, the Department is developing unique clinical trials to improve the treatment and care of children with cancer. Leading Dana-Farber's pediatric clinical trials program is Carlos Rodriguez-Galindo, MD. The Department's clinical trials portfolio includes investigator-initiated, cooperative group, and company-sponsored trials for a variety of cancers at different stages of progression.

Vulnerabilities in leukemia stem cells

Scott Armstrong, MD, PhD, is focusing on acute myelogenous leukemia associated with chromosomal rearrangements of the MLL gene, an infant leukemia that is difficult to treat. His laboratory has shown that the MLL fusion products promote the formation of a self-renewing cell population called leukemic stem cells. These cells, which sustain the leukemia, express genes normally restricted to immature blood stem cells. Armstrong and colleagues are now examining ways to target these differentially expressed genes. Such approaches may lead to novel therapies.

Attacking brain tumors

Mark Kieran, MD, PhD, and Charles Stiles, PhD, co-chair of Cancer Biology, created the Pediatric Low-Grade Astrocytoma Program at Dana-Farber. Believed to be the first coordinated effort focusing on low-grade gliomas, the program has a five-year objective to identify a molecular target that can be affected with personalized therapy.

Rosalind Segal, MD, PhD, who is also a member of Cancer Biology, is studying the pathways by which extracellular stimuli (such as growth factors and cell-to-cell interactions) regulate development. Segal and her group have demonstrated that neuronal precursors in the cerebellum migrate along a gradient of the growth factor brain-derived neurotrophic factor (BDNF). The lab has identified critical intracellular pathways that allow this migration and is identifying new ways in which these pathways can be selectively turned on or off. Recent studies have highlighted a role for the BDNF receptor in diverse metastatic diseases. Thus, Segal's studies may lead to new cancer drugs that block cancer cell dissemination.

New approaches to sarcoma research

Charles Roberts, MD, PhD, is studying the role of the SWI/SNF protein complex in malignant rhabdoid tumors and other cancers. He is also investigating the mechanisms by which it controls cell growth. Roberts and his group found that aggressive cancers that arise in mice deficient in the SNF5 gene lack widespread genome mutations. The changes that occur following SNF5 mutation are actually epigenetic alterations, which are potentially reversible and, therefore, have important therapeutic implications for a wide variety of cancers.

Stuart Orkin, MD, is leading an effort to find new approaches to osteosarcoma, the most common primary bone tumor, using an engineered mouse model that mimics the human cancer. His team, along with Katherine Janeway, MD, seeks to define the pathways leading to metastasis and to identify novel agents that may promote differentiation of the cancer cells.

Advancing our understanding of neuroblastoma

Rani George, MD, PhD, performed a genome-wide analysis of neuroblastoma tumors and found multiple copies of a receptor tyrosine kinase gene, ALK, in up to 14 percent of high-risk neuroblastomas. In collaboration with the Broad Institute, George sequenced ALK in 93 primary neuroblastoma tumor samples. She discovered five different mutations, with one mutation recurring in four cases.

Genomic approaches to drug discovery

Kimberly Stegmaier, MD, focuses on genomic approaches to drug discovery. With the Broad Institute, Stegmaier developed a new method of chemical discovery called gene expression-based high-throughput screening (GE-HTS). This technique led to the discovery of chemicals that induce the maturation of acute myeloid leukemia (AML) cells and resulted in a clinical trial for patients with relapsed AML. Many malignancies are believed to arise from the abnormal proliferation of cells and the failure of primitive cells to differentiate. For this reason, Stegmaier is focusing on the differentiation defect in two model diseases, AML and neuroblastoma.

Aneuploidy: attacking differences in cancer cells

David Pellman, MD, recently developed a genome-wide imaging approach to identify genes that are essential for abnormal cell division. His goal is to find genes that are not necessary in normal cells, but are required for the survival of cancer cells. One way to distinguish cancer cells from their normal counterparts is the presence of too many centrosomes. These are cellular structures that initiate the cellular machine that distributes the chromosomes in a dividing cell. This study identified a novel drug target, the kinesin HSET. Blocking HSET kills neuroblastoma cells with extra centrosomes, but spares normal cells. This information may impact the treatment of leukemias and solid tumors, where increased centrosome numbers are common.

Chemical biology: a new frontier of multidisciplinary medicine

Loren Walensky, MD, PhD, is applying novel compounds to dissect and manipulate the cell signaling pathways that are integral in apoptosis in order to reactivate them to overcome cancer. Walensky inserted a chemical "staple" into a natural but otherwise unstable cell-killing peptide. This reactivated the apoptosis cell signaling pathway in leukemia cells. When the stapled peptide was injected into mice, it suppressed human-type leukemia. Compounds such as this one are now being used to study the interactions of proteins inside cells, giving scientists a "molecular toolbox" to study and to potentially treat cancer and other diseases.

Harnessing the immune system to fight cancer

William Nicholas Haining, BM, BCh, is identifying the molecular characteristics of T cells associated with immunologic protection. Using gene expression profiling, Haining has demonstrated that all lymphocyte lineages in mice and humans use a common cell differentiation program during memory development. With Stegmaier, he has used GE-HTS to identify small molecules, genes, or soluble factors that direct memory differentiation in naive human lymphocytes. These studies may lead to the discovery of new immunomodulatory drugs or vaccine strategies.

Aberrant signal transduction in cancer

Andrew Kung, MD, PhD, is studying the mechanisms through which the hypoxia-inducible factor pathway allows cells to adapt to hypoxia. He is also focused on how to therapeutically target hypoxic tumor cells. Kung has developed new ways to use noninvasive imaging in order to assess molecular pathways within tumors, and has used these approaches to validate new therapies in mouse models. Kung leads the new Dana-Farber Lurie Family Imaging Center and helped establish the Institute's Center for Biomedical Imaging in Oncology