Grants Search Results

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that requires treatment with highly intensive chemotherapy. The prognosis of patients with relapsed and refractory (treatment resistant) T-ALL is very poor. Dr. Ferrando and his team have identified that specific mutations in the NT5C2 gene lead to chemotherapy resistance in 20% of relapse T-ALL cases. The goal of this research is to generate a model of chemotherapy resistance driven by mutant NT5C2 genes and utilize this model to develop new tailored therapies for the treatment of relapsed T-ALL.      

Hypodiploid acute lymphoblastic leukemia (ALL), in which the leukemic cells have lost multiple chromosomes, is associated with poor outcome. Dr. Mullighan and his team identified multiple new gene mutations that have not previously been recognized in this disease. Dr. Mullighan is investigating the impact of the identified mutations on leukemia formation, and investigating therapeutic alternatives for this high-risk leukemia. PI was initially Dr. Linda Holmfeldt.

Human synovial sarcoma is uniformly driven by a precise genetic lesion (change to our heritable material, or DNA), which converts a normal protein into one that functions abnormally and promotes cancer development. This research aims to identify molecules which prevent this conversion and halt synovial sarcoma growth.

Alveolar rhabdomyosarcoma is an aggressive childhood cancer that often arises in muscle. It contains a DNA error which drives cells to divide when they shouldn't, resulting in cancer. Dr. Linardic has discovered one targetable protein that is controlled by this DNA error. Her work aims to understand how this protein and the DNA error associated with Alveolar Rhabdomyosarcoma are related, and whether the protein she discovered will be a useful drug target.

Although radiation is a known carcinogen whose effects are most pronounced in children, it is ubiquitous in modern life. By studying survivors of pediatric Hodgkin lymphoma, Dr. Onel's team discovered that genetic variants regulating one gene are both very common and strongly associated with increased risk for radiation-induced cancers. Dr. Onel and his team are working to determine how radiation activates this gene, how the gene directs the response to radiation, and how variants alter this response. Dr. Onel hopes that these results will lead to new ways to identify children at risk for radiation-induced cancers, or new drugs to prevent this devastating late effect of radiation exposure.

Medulloblastoma is the most common malignant brain tumor. There is an urgent need to develop novel therapies for children with medulloblastoma. Dr. Van Meir and his team are studying the importance of the loss of tumor suppressor BAI1 in medulloblastoma. Such new knowledge has the potential to reveal new ways to treat this disease.

Many currently used chemotherapeutic drugs have severe toxic side effects and a significant number of cancer patients do not respond well to chemotherapy. Thus, developing more effective and less harmful new anticancer drugs remains significant and challenging. Dr. Zhou's team has discovered several small molecule chemical compounds that are stronger to kill cancer cells, and less toxic to normal cells than currently used chemotherapeutic drugs. Dr. Zhou is studying the mechanism by which these compounds kill cancer but not normal human cells, and how to develop these compounds as effective and safe therapeutic drugs for treating refractory cancer patients.

Neuroblastoma is a common childhood cancer. Cancers happen because of mutations (mistakes) in the genetic code within them, and knowing which specific mutation happened in each particular cancer should help doctors improve their treatments. Dr. Hogarty's team discovered that some neuroblastomas have mutations in a specific gene, ARID1, and that these tumors are especially difficult to cure. Dr. Hogarty is studying this gene more since it determines how nerve cells behave, and neuroblastoma arises from mutated nerve cells. This may give us insight into new ways to treat neuroblastoma.

Recurrence of childhood Acute Myeloid Leukemia (AML) is all too frequent after initially successful treatment. The underlying drug resistance is partly related to the protective role of the bone marrow microenvironment, where leukemia cells grow. Dr. Kurre's team has recently discovered that AML cells release small amounts of material in the bone marrow microenvironment that cause changes to promote leukemia progression. Dr. Kurre is working to better understand these changes and how these changes can reprogram the leukemia bone marrow to protect residual AML cells and lead to relapse.

Neuroblastoma is a pediatric tumor that is very difficult to treat, even with surgery and chemotherapy, because certain genes in these cancer cells are over-expressed. Dr. Malkas and her team have identified a protein that is uniquely expressed by these cancer cells, and discovered that a small portion of this protein can be used as a decoy to bind-up other proteins to selectively kill cancer cells. She is working to determine how this protein kills tumor cells, and how to make the cells more sensitive to chemotherapy.

Medulloblastoma is the most common malignant brain tumor in children. These tumors are caused by or associated with two proteins which cannot be directly attacked with drugs. However, these proteins rely on other proteins involved in the translation (the process of making more proteins) to cause cancer. Currently researchers can alter translation with drugs in clinical trials for adult cancers. Dr. Weiss's team is trying to determine how these two proteins rely on these translational proteins in medulloblastoma, and how to modulate them with currently available drugs, to halt tumor growth and destroy tumor cells.

Rhabdoid tumors are highly aggressive cancers that strike young children, for which a cure still remains elusive. In nearly all cases of rhabdoid tumors a specific tumor gene (SNF5) is mutated. But how this mutation drives rhabdoid tumor formation remains largely unknown. Dr. Wang's research investigates how this mutation eventually predisposes to cancer formation, with the ultimate goal of translating these findings to find potential therapies for this aggressive pediatric cancer. This research is funded by P.A.L.S. Bermuda with funds raised through the St. Baldrick's Foundation.

NUT midline carcinoma is a deadly cancer of children and adolescents. This cancer is caused by a cancer gene called BRD4-NUT, but it cannot work without the help of other cancer genes. BRD4-NUT itself cannot be targeted very effectively with known cancer drugs. Dr. French is working to identify the cancer genes that are helping BRD4-NUT so that we can effectively treat NUT midline carcinoma with drugs that interfere with these cancer genes.    

Dr. Aifantis's laboratory is studying T-cell acute lymphoblastic leukemia (T-ALL), a devastating pediatric tumor of the blood. This tumor is characterized by frequent relapses and no cure has been found so far. This lab was one of the first to identify a single gene, Notch1, that is mutated and activated in the majority of T-ALL cases. In this project, Dr. Aifantis studies the way that this gene is regulating disease induction and progression, and tests novel inhibitors of the Notch signaling pathway, hoping that one of them can efficiently suppress T-ALL both in the laboratory and in clinical trials.

Ewing sarcoma relies on a gene called EWS-FLI1 to grow and spread throughout the body. Studies have previously shown a drug called ET-743 turns this gene off. In this work, Dr. Grohar's lab is trying to find drugs similar to ET-743 that may turn off EWS-FLI1 more effectively. In addition, they are looking to see if shutting down this gene creates a sensitivity to other chemotherapeutic drugs, especially the combination of ET-743 and a drug called irinotecan, which may be particularly effective at treating Ewing sarcoma.

Acute lymphocytic leukemia (ALL) is the most common form of childhood cancer, with about 3,000 new cases in the U.S. per year. The leukemia cells in a patient can become resistant to the drugs used to treat disease, which results in a poor outlook for these children. This study tests a new therapeutic agent (Leukothera®) that specifically eliminates leukemia cells for the treatment of children with ALL.

The overarching goal of this research is to develop a non-invasive technique for cancer therapy. This technique uses High-Intensity Focused Ultrasound (HIFU) to deliver therapy, and Magnetic Resonance (MR) guidance to monitor therapy. MR-guided HIFU enables "surgical procedures" to be performed deep within the body without incisions or punctures, providing a risk-free approach to the treatment of adolescent and childhood cancers. This study aims to overcome a fundamental challenge: How can we use MR-guidance to control HIFU therapy with the individual variations between patients.

Biomarkers are small molecules that can be detected in the body fluids of patients; they often correlate with the presence of a cancer. MicroRNAs are small molecules which have recently been discovered in cells and are responsible for normal development as well as cancer. Recently, microRNAs from tumor cells have been detected circulating in the blood, spinal fluid and urine of patients with cancer. This project aims to identify the microRNA biomarkers in the body fluids of children with brain and spinal cord tumors, which may be valuable as biomarkers of cancer and response to treatment.

Dr. Nicolaides is investigating a new combination of treatments for pediatric brain tumors. Malignant astrocytomas (MA's) are an aggressive and often incurable group of brain tumors. Recent evidence suggests that a fraction of these tumors contain a mutant form of a key growth promoter in the cell- BRAF-V600E. A drug that blocks the function of this cell has recently shown dramatic efficacy in melanomas and has been FDA approved. This drug shows some effect against MA's with BRAF-V600E, however the response is only temporary. In early studies, it has been shown that another pathway (EGFR) may be responsible for this resistance, and this project aims to target the EGFR and BRAF pathways simultaneously to improve effectiveness of the drug.

High levels of the receptor for a specific growth factor have been linked to a type of leukemia where children have a poor survival rate. This project studies the role of the growth factor that stimulates this receptor in the progression of leukemia. Understanding the contribution of the growth factor and its receptor to disease will help researchers develop drugs that can target these molecules and increase survival in children with leukemia.