Grant: 6505-17 | Translational Research Program (TRP):
Location:Children's Hospital Los Angeles, Los Angeles, California 90027
Project Title: Overcoming Drug Resistance In Leukemia Using A Novel Integrin Alpha4 Inhibitor, AVA-4746.Project Summary:
The prognosis of adults treated for ALL is very poor with an overall survival rate of only 40%. Although many children who are treated for acute lymphoblastic leukemia (ALL) are cured, a significant percentage is not, and when this happens the prognosis is grim. Therefore, we need new ideas for treatment of relapsed ALL. Instead of targeting only the leukemia cells, we look at a wider target: the leukemia cells as well as the protective non-leukemia cells that are located in the bone marrow creating a safe haven for ALL cells.
Grant: 6518-17 | Translational Research Program (TRP):
Location:University of Alabama at Birmingham, Birmingham, Alabama 35294-0111
Project Title: Optimizing Small Molecule Inhibitors Of Heparanase For Myeloma TherapyProject Summary:
Heparanase is an enzyme that is present in high levels in myeloma tumors and its presence is associated with poor patient prognosis. In laboratory studies, when heparanase was present it was shown to promote aggressive myeloma tumor growth, but when heparanase was absent the tumors grew very poorly. These findings suggest that blocking heparanase in myeloma patients will interfere with tumor growth. Although there are several heparanase inhibitors currently available, none of them are specific for heparanase and thus will likely have side effects that could harm patients.
Grant: 6509-17 | Translational Research Program (TRP):
Location:Massachusetts General Hospital, Boston, Massachusetts 02241-4876
Project Title: Developing Brequinar, An Inhibitor Of DHODH, As Differentiation Therapy In Acute Myeloid LeukemiaProject Summary:
Of 10 adults diagnosed with acute myeloid leukemia (AML), only 3 are alive five years later. We now know that AML is not just one disease, but that it is really a complicated family of many different types of leukemia. As one can imagine, this means that each patient’s leukemia is unique, which makes the development of new therapies even more difficult.
Grant: 7011-16 | Specialized Center of Research Program (SCOR):
Location:Dana-Farber Cancer Institute, Boston, Massachusetts 02215
Project Title: Translational Discovery In Peripheral T-Cell LymphomasProject Summary:
T-cell lymphomas (TCLs) are very poorly understood and patients with these diseases have few treatment options. Our groups and others recently identified mutations in some TCLs that drive their growth. At the same time, clinical trials have identified drugs that can shrink TCLs in some patients. We propose a Specialized Center of Research (SCOR) that builds on these advances to engender meaningful improvements in the treatment of TCLs. The SCOR consists of three innovative and highly interconnected research projects that focus on pressing questions relevant to TCL treatment.
Grant: R6505-17 | Translational Research Program (TRP):
Location:The Regents of the University of California, San Francisco, San Francisco, California 94143
Project Title: Precision Medicine In CNS Lymphoma: Targeting NFkB Activation PathwaysProject Summary:
We have recently discovered two genetic subtypes of primary and secondary CNS lymphomas: a non-invasive subtype that is typically localized within one area of the brain, as well as an invasive subtype that is typically multifocal, and disseminated to multiple sites within the brain, including the cerebrospinal fluid. Furthermore we determined that the multifocal, invasive type exhibits selective activation of genes known as the NFkB pathway that promotes tumor invasion, metastasis and drug resistance.
Grant: 7012-16 | Specialized Center of Research Program (SCOR):
Location:Weill Cornell Medical College, New York, New York 10022
Project Title: Targeting Unmet Clinical Needs For B-Cell LymphomasProject Summary:
Approximately half of lymphoma patients cannot be cured, and even those who are cured must endure significant toxic chemotherapy effects. We lack a full understanding of what makes certain lymphomas resistant. Hundreds of new drugs becoming available are supposed to hit specific molecular targets in lymphomas. However, the task of comparing and contrasting their activity in human lymphomas or models relevant to human lymphomas is daunting since there are thousands of possible dose schedules and combinations. Moreover, we have no way to monitor the activity of most drugs in humans.
Grant: 6503-17 | Translational Research Program (TRP):
Location:The Ohio State University, Columbus, Ohio 43210
Project Title: CS1 Chimeric Antigen Receptor (CAR) T Cells For Treatment Of High-Risk Multiple MyelomaProject Summary:
Multiple myeloma (MM) is the second most frequent blood cancer in developed countries, with effective treatments for most, but those patients with high-risk disease will quickly succumb to the disease. Unprecedented success has recently been reported in other blood cancers with the use of cellular therapeutic targeting via the technology “chimeric antigen receptors (CAR)”, involving the infusion of genetically engineered T cells, which are targeted towards proteins on the tumor cell surface, into relapsed patients.
Grant: 2315-17 | Career Development Program (CDP):
Location:Beckman Research Institute of City of Hope, Duarte, California 91010-3000
Project Title: Cardiovascular Reserve Capacity In Survivors Of Hematopoietic Cell TransplantationProject Summary:
Hematopoietic cell transplantation (HCT) is the treatment of choice for many hematologic malignancies such as acute leukemia and lymphoma. During the past four decades, there have been tremendous advances in HCT, contributing to a growing number of long-term survivors of living in the U.S. today. However, these survivors are at risk for severe and life-threatening complications that can significantly impact quantity and quality of survival.
Grant: 5459-17 | Career Development Program (CDP):
Location:University of California, San Francisco, San Francisco, California 94143
Project Title: Local Delivery Of Therapeutic Cytokines Via Engineered T Cells In Immunocompetent Mouse Models Of CancerProject Summary:
Lymphomas are malignant tumors derived from lymphocytes, blood cells responsible for fighting infection. Peripheral T-cell lymphomas are some of the most aggressive and difficult to treat forms of this disease. As a result, they are frequently associated with very poor prognosis. We propose that improved understanding of the mechanisms implicated in this disease will facilitate the development of new and more effective therapies. In this context, we have identified mutations in the VAV1 gene in lymphoma samples from peripheral T-cell lymphoma patients.
Grant: 3368-17 | Career Development Program (CDP):
Location:Memorial Sloan Kettering Cancer Center, New York, New York 10087
Project Title: Identifying Therapeutic Vulnerabilities In Spliceosomal-mutant MalignanciesProject Summary:
In recent years, a new class of genetic mutations was discovered in a wide variety of leukemias that have changed the way clinicians and scientists view how leukemia develops. These mutations affect genes that encode proteins that splice RNA and are often some of the earliest mutations found in leukemia patients. They are also very common in forms of leukemia such as myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL), which makes them very attractive for targeted therapies.