Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

44 Binney Street

Boston, MA 2115

United States

A Translational Approach to Identify Drugs with Specific Activity Against EZH2 Mutant High Risk T-ALLs and ETP ALLs that Overexpress the JDP2 bZIP Transcription Factor

Leukemia, Acute Lymphoblastic Leukemia (ALL)

Background

Outcomes for children with acute lymphoblastic leukemia (ALL), the most common childhood malignancy, have improved dramatically over the last 20 years. However, a subset of patients with ETP-ALL have an extremely poor prognosis. Very recently, it was discovered that many of these high-risk tumors and other high-risk T-ALLs have acquired disruptions of the EZH2 gene. We have shown that the JDP2 gene is upregulated in both ETP-ALL and other high-risk T-ALLs and is required for the growth and survival of these leukemia cells.

The Role of PARP3 in the Formation of Chromosomal Translocations

Ewing Sarcoma, Acute Lymphoblastic Leukemia (ALL), Non-Hodgkin Lymphoma

Background

Cancer cells have many abnormalities in their DNA. In a cell, DNA is divided into large structures called chromosomes. Chromosomes can be broken as a result of exposure to damaging environmental factors such as sunlight or cancer treatments such as chemotherapy. Broken chromosomes are very dangerous to the cell because essential genetic information can be lost or corrupted, ultimately resulting in death of the cell. Ideally, a cell with broken chromosomes is able to correctly rejoin the broken ends to restore the chromosomes to their original form.

Therapies for SHH-subtype Medulloblastoma

Brain Tumors, Medulloblastoma

Background

Brain tumors are now the leading cause of cancer death in children. One of the most common brain tumors in children is called medulloblastoma. Many mutations (changes in the DNA) that cause medulloblastoma have been identified, and a new type of specific, targeted therapy looks very promising for attacking tumors with particular mutations. However, some tumors with these mutations do not respond to the new specific drugs.

Role of LMO1 in Neuroblastoma Initiation and Maintenance: Analysis in the Zebrafish model of Childhood Neuroblastoma

Neuroblastoma

Targeting MYC/MYCN-driven Transcriptional Amplification in Pediatric Cancer

General Pediatric Cancer, Neuroblastoma

Understanding and Preventing Healthy Tissue Damage in Pediatric Cancer Patients

Brain Tumors, Medulloblastoma, Leukemia

Background

Treatment of human cancers with chemotherapy or radiation has led to the successful eradication of malignancies in millions of patients, yet the cell death induced in healthy tissues drastically limits the use of these crucial therapies. This is especially true in pediatric patients who experience more damaging side effects from treatment. For example, children with many types of cancers are commonly treated with doxorubicin, which is an extremely effective anti-cancer agent and cures many patients.

Translating BET Bromodomain Inhibitors for Acute Myeloid Leukemia Therapy

Leukemia

Background

Acute myeloid leukemia (AML) accounts for 20% of childhood leukemia and has a long-term survival of only 50%. Thus, new therapies are urgently needed. A new class of drugs, BET bromodomain inhibitors, target proteins that regulate the architecture of DNA and hold significant promise for treatment of pediatric leukemia. At the same time, the relevance of altered metabolism in AML has also come to the forefront. Much work is still needed to effectively implement these discoveries in the clinic.

SETD2 Mutations in Prognosis and Chemotherapy Resistance in Relapsed Acute Lymphoblastic Leukemia

Leukemia

Background

Despite substantial improvements in the treatment of pediatric acute lymphoblastic leukemia, relapse still occurs in 15% of children and 50% of infants, with particular subgroups at substantially higher risk. In contrast to newly diagnosed ALL, patients with relapsed ALL have substantially worse rates of long term survival, reflecting the acquisition of or selection for leukemia cells with chemotherapy resistance.

Mechanisms of CNOT3 Tumor Suppression in T-ALL and Identification of New Drugs That Specifically Kill CNOT3-Deficient T-ALL Cells

Leukemia

Background

Acute Lymphoblastic Leukemia (ALL) is the most common leukemia among children making up 80% of all childhood leukemia cases. Among acute leukemia, T-cell acute lymphoblastic leukemia (T-ALL), which accounts for about 15% of pediatric cases, is aggressive hematologic tumors arising from progenitor cells that meant to become T cells. Understanding the biology of T-ALL may identify new targets for T-ALL therapy and open the way for the development of new drugs.

Analysis of the Deviations in the Diagnosis and Treatment Trajectories of Children with Cancer in Low-income Countries and Their Impact on Outcomes: A Comparative Study Between US and Guatemala

Rhabdomyosarcoma

Alex's Lemonade Stand Foundation for Childhood Cancer