Oncology

Research Activities

WOLF Foundation Leukemia/Lymphoma Laboratory

The laboratory of Adolfo Ferrando, MD, PhD in conjunction with Drs. Maria Luisa Sulis and Theresa Palomero seeks to understand the molecular mechanisms that promote and sustain the malignant proliferation and survival of leukemic cells. The lab’s research is focused on the cellular and molecular biology of T-cell lymphoblastic leukemia, an aggressive malignancy that results from the cancerous transformation of the progenitors that normally generate the cellular elements of the immune system. Their team is analyzing the functions of specific oncogenes such as NOTCH1 and the tumor suppressor gene PTEN to define their role in the origin of childhood leukemia and lymphoma using a combination of genomic technologies, biochemical and genetic analysis. They are also studying the role of deletions in the short arm of chromosome 11 in the pathogenesis of pediatric leukemia. The Ferrando lab receives support by a grant from the Leukemia and Lymphoma Society and by R01: CA120196-01A1: Mechanisms of T-cell Leukemogenesis Induced by Notch1


Brain and Nervous System Tumor Laboratory

The laboratory of Anna Lasorella, MD and Antonio Iavorone, MD a husband and wife team, is dedicated to research in brain tumors and other tumors of the nervous system including neuroblastoma. Their work focuses on the deregulation of the cell cycle and the differentiation in tumors derived from the brain and nervous system. The Lasorella & Iavarone team has determined that the retinoblastoma (Rb) tumor suppressor protein restrains Id2 activity in normal and cancer cells. Loss of Rb results in deregulated Id2 activity with inhibition of differentiation and induction of cell proliferation. Id2 is required at multiple stages of tumorigenesis initiated by loss of Rb including tumor angiogenesis. A specific goal of the laboratory is to identify the molecular events directly engaged by Id2 to prevent differentiation and enhance cell cycle progression, to establish the role of Id proteins in progression of human cancer of the nervous system and attempt to identify anti-Id molecules to be used as targeted therapeutic tools for these diseases. The laboratory is supported by grants from the Brain Tumor Foundation and by NCI R01-CA101644: the Rb-Id2 pathway in mouse development and tumorigenesis and NIH/NCI R01-CA85628: Id2 in cell cycle regulation and cancer.


Taybanz/ Matthews Family Foundation Solid Tumor Laboratory

The Pediatric Tumor Biology lab is a joint research effort of Dr. Darrell Yamashiro of Pediatric Oncology and Dr. Jessica Kandel of Pediatric Surgery. The main focus of their research is to understand the biology of pediatric solid tumors. Drs. Yamashiro and Kandel have used investigations of tumor blood vessel growth, or angiogenesis, as a lens to illuminate the fundamental steps of tumor progression, metastasis, and resistance. Work in the laboratory has shown that pediatric tumors make an essential protein called vascular endothelial growth factor (VEGF), and that treatment with the anti-VEGF antibody Bevacizumab (AvastinTM, Genentech) or the novel VEGF blocking agent VEGF-Trap (Regeneron Pharmaceuticals) can dramatically inhibit growth of experimental models of pediatric tumors such as neuroblastoma, Wilms tumor, and hepatoblastoma. As a direct result of this research, Dr. Julia Glade Bender of Pediatric Oncology led the first pediatric clinical study with Bevacizumab. This nationwide study focused on children with relapsed solid tumors, and was sponsored by the National Cancer Institute and the Children’s Oncology Group. The solid tumor lab is supported by the following grants: NIH 1 R01CA088951, The role of neurotrophin receptors in neuroblastoma; NIH 1 R01CA100451, Acquired Resistance to VEGF Blockade in Wilms Tumor; NIH K08 CA107077, Role of angiopoietins in Wilms tumor; NIH 1R01-CA124644-01, VEGF blockade and alternative angiogenic pathways in neuroblastoma,


Molecular Epidemiology

The molecular epidemiology laboratory of Dr. Manuela Orjuela is involved in three separate, but inter-related projects that investigate the root cause of childhood cancer secondary to genetic and environmental interactions. The first project is investigating folate deficiency and genetic variation in folate metabolism and the development of sporadic unilateral retinoblastoma in children. The aim is to determine whether mothers of children with sporadic retinoblastoma, have a greater incidence of less functional forms of the genes that encode the folate metabolizing enzyme MTHFR and whether this increased risk for having a child with retinoblastoma varies depending on levels of plasma folate, and plasma homocysteine, an amino acid which is involved in its metabolism. Second, Dr. Orjuela and her colleagues are involved in studies to explore the role of prenatal exposures to procarcinogenic polyaromatic hydrocarbons (PAH) during pregnancy on the development of chromosomal aberrations (deletions and translocations) detectable in cord blood. Third, Dr. Orjuela, in collaboration with Dr. Kara Kelly and investigators at the Dana Farber Cancer Institute are investigating metabolizing enzymes, dietary intake, toxicity and the event free survival (EFS) in children with acute lymphoblastic leukemia to determine if a gene-nutrient interaction exists. Dr. Orjuela’s work is supported by the following: Prenatal Exposures and Procarcinogenic mutations in newborns: ES12732-01; American Cancer Society RSG 03008-01-CNE; NIH/NCI R01 CA098180 Folate Deficiency, Metabolism, and Sporadic Retinoblastoma 1 R01 CA098180.


Clinical Research

Center for Survivor Wellness

Center for Survivor Wellness The CSW has a strong commitment to performing research to advancing our understanding of survivorship and the late effects of being cured of childhood cancer. The center participates in projects that are intramural, extramural, and those that accrue data as part of national cooperative group studies. Presently, Dr. Jennifer Levine and her associates are involved in the following projects:

• Late Effects of Hodgkin's Lymphoma: a national study under the auspices of the Children's Oncology Group
• Use of statins to decrease risk for the late development of cardiovascular disease
• Evaluation of ovarian reserve in survivors of Hodgkin's disease
• Qualitative analysis of barriers to long-term follow-up
• Assessment of needs as patients complete therapy
• Survey of the use of complementary and alternative medicine in survivors of pediatric cancer
• Survivor Transition Intervention, a study funded by the Susan G. Komen Foundation investigating how lifestyle information creates transformative change in behavior in breast cancer survivors

• phase I/II study of topotecan by intracerebral clysis – a system that delivers drugs directly to the site of a brain tumor – for treatment of recurrent brain tumors
• identification of brain tumor cell migratory motor proteins as targets for investigational therapies
• erlotinib/etoposide for recurrent brain tumors Physicians here are also studying the treatment outcomes in children with germ cell tumor, including chemotherapy for patients with newly diagnosed germ cell tumors of the central nervous system and high dose chemotherapy with bone marrow reconstitution for patients with recurrent germ cell tumors.