Massachusetts General Hospital

55 Fruit Street

Boston, MA 2114

United States

Multifunctional Nanomaterials for the Prevention of Radiotherapy's Side Effects and Childhood Cancers

Background

Each year, hundreds of children undergo radiation therapy, in order to treat their primary cancer. Due to radiation's potency and in the absence of highly effective protection systems, these children may suffer brain damage and experience developmental problems. Also, radiation can affect their skin and bone marrow, causing skin cancer and leukemia.

A Role for Notch in Self-renewal in Embryonal Rhabdomyosarcoma

Rhabdomyosarcoma

Tumor relapse is the major clinical problem facing patients diagnosed with embryonal rhabdomyosarcoma (ERMS), a childhood malignancy of the muscle. Sadly, greater than 50% of patients with relapsed RMS will ultimately succumb to their disease. Recent advances in DNA sequencing technologies have identified a common spectrum of genetic changes that are associated with different types of tumors, although only a subset are present among individual patients. This variation likely results in different responses to drug treatments.

Targeting the Mechanism of Differentiation Arrest in a Novel Model of Acute Leukemia

Leukemia

Infant acute leukemias (arising in children less than one year old) makes up a unique subset of leukemias that are particularly lethal and that are characterized by recurrent mutations in one gene. This gene has been termed the mixed lineage leukemia (or MLL) gene, and mutations in MLL are found in the majority of infant leukemias as well as in smaller proportions of childhood and adult leukemias. The mutations in MLL are intriguing, because they are the result of chromosomal breakage which abnormally joins the MLL gene to a variety of partner genes.

The Role of Metabolism in MLL-AF9 Leukemia Initiation

Acute Myeloid Leukemia (AML)

It has been shown that metabolism, which comprises a range of biochemical processes essential for cell functioning, can play a role in the causation of cancer including leukemias. Certain leukemia cells have been shown to have cancer initiating or 'stem cell' potential. There is little knowledge about the role that metabolism plays in the maintenance of leukemia stem cells.

TLE1 Tumor Suppressor as a Key Regulator of myc Induced Leukemia

Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML)

Research in pediatric cancer over last 30 years has led to improvements in the treatment and cure rate for most of the pediatric cancer. Despite improvement in the pediatric patient survival over the last decades, still about 30-40% of children die of cancer and also many treatments affects the quality of the life. There is a need for identification of new targets and anti-cancer agents to improve the survival and quality of life. TLE1 gene is a novel tumor suppressor and co-repressor gene that is deleted or methylated in acute myeloid leukemia (AML) and other hematological malignancies.

Identification of FDA approved drugs with anti-tumor activity in rhabdomyosarcoma.

Rhabdomyosarcoma

This project will uncover genetic pathways and FDA approved drugs that have novel anti-tumor activity in a rare, pediatric malignancy of muscle -- embryonal rhabdomyosarcoma (ERMS). Rhabdomyosarcoma effects over 250 patients annually in the United States, of which ERMS is the most common subtype. Our work has already identified a key genetic pathway involved in ERMS tumor growth, the RAS pathway.

A mouse model of Wilms' Tumor

Wilms Tumor

Background

The pediatric kidney cancer, Wilms tumor, is the fourth most common type of cancer in children. Wilms tumor seems to arise because of abnormalities in the formation of the kidneys from primitive cells in the embryo. The most studied genes mutated in Wilms tumor include WT1 and beta-catenin, which are essential for controlling the development of normal kidneys and in controlling how cells divide. However, these genes are only mutated in a small percentage of Wilms tumors.

Alex's Lemonade Stand Foundation for Childhood Cancer