Massachusetts General Hospital

55 Fruit Street

Boston, MA 2114

United States

Identifying Epigenetic Mechanisms Impacting Neuroblastoma Genome Stability and Drug Response

Background

Genome instability and drug resistance are hallmark features of cancer, especially neuroblastoma. We have recently uncovered the first enzyme KDM4A capable of generating site-specific copy gains of regions linked to drug resistance and hard to treat cancer, which provides a novel tool to carefully interrogate the molecular features affiliated with copy gains.

Anti-PIGF Therapy in Medulloblastoma

Brain Tumors, Medulloblastoma

Background

Medulloblastoma is the most common childhood brain tumor. It arises in the cerebellum, the part of the brain that controls coordination and movement. The standard treatment regimen consists of surgery, followed by a combination of intensive radiation and chemotherapy. Radiation therapy of the central nervous system in children is associated with severe side effects, including impaired cognitive function, neuroendocrine dysfunctions and secondary cancers. Currently, there is no treatment for resistant or relapsing tumors.

Modeling the Multi-hit Pathogenesis of t(12;21) Associated Pediatric ALL by CRISPR/Cas-mediated Genome Engineering

Acute Lymphoblastic Leukemia (ALL)

Proton Radiation Therapy for Pediatric Brain Tumors: Correlating Dose, Neuroanatomy, and Neurocognitive Outcomes

Brain Tumors

Novel Strategy for Reducing Radiation-Induced Morbidity and Treating Recurrent Medulloblasoma

General Pediatric Cancer

Medulloblastoma is the most common malignant pediatric brain tumor. Current standard of the care of medulloblastoma is a combination of chemotherapy and radiation therapy. While this aggressive treatment regiment can potentially cure the disease, treatment-induced morbidities are devastating and furthermore, one third of patients relapse despite the treatment. Currently, there are no alternative therapies available for patients with recurrent tumors.

Novel Therapeutic Targets in Relapse T-cell Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL)

Background

The aggressive and unpredictable behavior of relapsed T-cell acute lymphoblastic leukemia (T-ALL) presents a major clinical challenge, as relapsed disease continues to have a dismal prognosis in both children and adults. A major hurdle in the development of new chemotherapies is identifying drugs that specifically kill malignant T cells, while leaving normal cells untouched.

PRL3 as a Novel Therapeutic Target for Relapsed T-cell Acute Lymphoblastic Leukemia

Leukemia

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

General Pediatric Cancer

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.

Alex's Lemonade Stand Foundation for Childhood Cancer