Grants Search Results

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.

Brain tumors are the leading cause of cancer-related death in children. Unfortunately, current treatments leave most children that survive with severe disabilities, due to the harsh and nonspecific nature of the therapy. In order to improve overall survival and minimize this toxicity, new treatments that specifically target cancer cells and spare surrounding normal non-cancer cells are needed. To achieve this, Dr. Praveen is working to test and optimize new therapies specifically against cancer cells and not surrounding normal cells.

Identical twins have the exact same DNA sequence. Epigenomic changes might cause freckles on one twin and not the other. Now we know that mutated genes in cancer alter the epigenome. Dr. Thiele is working to identify the epigenetic genes involved in stimulating neuroblastoma growth. Neuroblastoma accounts for over 10% of all deaths in children due to cancer. This project aims to turn off the expression of the different epigenetic genes in the tumor cells and determine which ones, when turned off, cause the tumor cells to stop growing. Then researchers can look for or design drugs that inhibit these genes, to stop tumor growth in patients.

Ewings sarcoma, the second most common bone cancer in children and young adults, is very aggressive. Current treatments are not very effective at curing the disease and patients often experience a recurrence of their cancer. Dr. Van Meir is looking for new and more effective treatments for this type of tumor. His laboratory has found a small molecule (KCN1) that they believe may reduce the growth of Ewings sarcoma. KCN1 binds with EWS-FLI1 which is known to stimulate the growth of Ewings sarcoma. Earlier attempts at using a recombinant EWS-FLI1 to produce targeted therapy have been difficult due to the lack of information about the structural makeup of EWS-FLI1. In this project researchers are investigating 1) How the binding occurs between EWS-FLI1 and KCN1, 2) Whether the KCN1 reduces the expression of the EWS-FLI1 gene that causes Ewings and 3) Does KCN1 interfere with Ewings sarcoma development.

Therapy for children with leukemia is difficult, prolonged, toxic and carries long term-side effects. Previous studies clearly show that the immune system can recognize and destroy leukemia. However, this process is inefficient. Dr. Verneris is working to design drugs that bring elements of the immune system in close contact with the leukemia. This has the immediate effect of killing the leukemia and the long-term potential of "training" the immune system to recognize and remember the leukemia. These drugs are now being tested in clinical trials with impressive results and this research will create more effective forms of this therapy.

Children with advanced cancer experience significant suffering. To improve their comfort, Dr. Wolfe aims to understand how distressing symptoms are evaluated and treated, and also to identify attitudes and behaviors in clinicians and families that may interfere with optimal symptom control. To do so, this project is carefully following what happens when a child reports high distress from pain and other common symptoms during clinic visits, as well as interview providers and families, and review charts. The results will help researchers improve symptom control and will be used to design the PediQUEST Champions intervention aimed at easing suffering in children with cancer.

This research is funded by P.A.L.S. Bermuda with funds raised through the St. Baldrick's Foundation.

Dr. O'Bryan is studying the signals that contribute to the development and growth of neuroblastoma tumors. His lab has found a new gene that is important for tumor growth. Although the gene is not useful for targeting treatment, the researchers are studying the ways that this gene works within the cell. With this information, they may be able to identify new drugs that interfere with its function thus interfering with the growth of neuroblastoma cells. This information may be useful in the development of new, more effective treatments for neuroblastoma patients.

Current treatments for kids with brain tumors don't work as well as they should and they have toxic side effects. Often these brain tumors and also other kinds of tumors outside the brain in kids are caused by mutations in a gene called N-Myc. Since researchers don't understand very well how N-Myc causes cancer, they can't fix it. The goal of this project is to test the idea that N-Myc mutations create bad cells called "cancer stem cells" that are like seeds that grow brain tumors. By testing this idea, Dr. Knoepfler and his lab hope to develop new treatments that are better and safer.

Diffuse Intrinsic Pontine Glioma (DIPG) and Medulloblastoma (MB) are the two most common malignant brain tumors in children, highly aggressive tumors that cause disability and death. A new concept in cancer biology is the cancer stem cell hypothesis, which states that tumors are initiated and maintained by a small fraction of cells with stem cell-like properties. This hypothesis could explain many of the mysteries of cancer biology, one of them being the recurrence of the same tumor despite aggressive radiation and chemotherapy. This study uses a computer program called MiDReg with DIPG and MB tumor samples to learn more and ultimately develop safer and better treatments.

T-cell acute lymphoblastic leukemia is an aggressive cancer that requires highly intensive chemotherapy, and the prognosis of patients with relapsed and refractory T-ALL is very poor. The genetic lesions responsible for progression and relapse in this disease remain largely unknown. The goals of this project are to identify novel pathogenic genes and pathways in relapsed and refractory T-ALL, to assess their contribution to T-cell transformation and chemotherapy resistance. These results will be ultimately translated in new diagnostic tools to identify high-risk patients and in new molecular targeted drugs for the treatment of this disease.