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.
Grant: 8009-17 | New Idea Award (NIA):
Location:Massachusetts General Hospital, Boston, Massachusetts 02241-4876
Project Title: Quiescence Induction By Angiogenin To Improve HSC Function In Bone Marrow FailureProject Summary:
Bone marrow failure (BMF) encompasses a variety of inherited and acquired conditions, which have a common defining feature - impaired ability of the bone marrow to produce blood cells Many important lessons about the biology of the BMF have been learned from studies in genetic animal models of rare human diseases, for example Fanconi anemia. Recent work in mice has shown that in this condition, the bone marrow is excessively "stressed" in response to outside challenges, such as infection or bleeding, and this might account for its inability to produce blood cells.
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: 6507-17 | Translational Research Program (TRP):
Location:The Trustees of Columbia University in the City of New York, Columbia University Medical Center, New York, New York 10027
Project Title: Bringing New Angioimmunoblastic T-cell Lymphoma Therapies To The ClinicProject Summary:
Angioimmunoblastic T-cell lymphomas are some of the most aggressive blood cancers. These tumors are highly resistant to current chemotherapy treatments resulting in cure rates of less than 30%. Classic approaches for the treatment of this disease have yielded little progress making the identification and testing of new highly active targeted drugs a priority. Importantly, our genomic analyses of patient samples have identified new specific genetic alterations characteristic of these high-risk lymphomas.
Grant: 6522-17 | Translational Research Program (TRP):
Location:University of Iowa, Iowa City, Iowa 52242
Project Title: Enhancing Lymphoma Checkpoint Blockade Immunotherapy By Local Modification Of The MicroenvironmentProject Summary:
Checkpoint blockade antibody therapy is showing great promise as a cancer immunotherapy. It blocks the ability of a cancer to turn off the immune system, and therefore allows the immune system (particularly T cells) to fight the cancer more effectively. Clinical trials in lymphoma using single agent checkpoint blockade antibodies show promise, but there is considerable room for improvement.
Grant: 1339-17 | Career Development Program (CDP):
Location:The University of Texas MD Anderson Cancer Center, Houston, Texas 77210-4266
Project Title: A Novel Epigenetic Target In MLL-translocated LeukemiasProject Summary:
Grant: 6516-17 | Translational Research Program (TRP):
Location:The University of Chicago, Chicago, Illinois 60637
Project Title: Overcoming Ibrutinib Resistance In CLL By Dual SYK/JAK Inhibition With A Single Agent CerdulatinibProject Summary:
Therapies targeting B-cell receptor (BCR) signaling pathway in CLL tumor cells, such as ibrutinib, are very effective with ~90% of patients responding to the drug initially. However, since the primary action of the drug is not cell killing, CLL cells, although under control, are not totally eliminated. The malignant cells then have an opportunity undergoing mutation and developing resistance to the drug then causing disease relapse. Once patients relapse, their outcomes are poor with only a few months of survival.