TCRF
Funded Research

  • Dual PI3K and BRD4 Inhibition as a Novel Therapeutic Strategy for Hepatocellular Carcinoma
    $100,000 Irving Feintech Family Foundation Career Development Grant

    Liver cancer is the second most common cause of cancer death worldwide, but the sole FDA-approved drug for liver cancer prolongs life for only 2-3 months and has significant side effects. While most anti-cancer drugs have a single target, we are investigating a novel drug, SF1126, that simultaneously targets two proteins (PI3K and BRD4) that are overactive in liver cancer, and our experiments demonstrate that it is efficacious and well tolerated. We are studying the mechanism whereby SF1126 kills liver cancer cells and are actively pursuing the use of dual PI3K/BRD4 inhibitors in clinical trials in liver cancer patients.

    Sponsor: Donald L. Durden, MD, PhD

    Adam Burgoyne, MD, PhD
    University of California, San Diego
  • Identification and Functional Analysis of PAX8 Binding Site Mutations in Ovarian Cancer
    $100,000 Magnolia Council Career Development Research Grant

    Epithelial ovarian cancers (OC) are highly lethal tumors, but treatment options are limited, largely because our poor understanding of the biology of OC development has hindered the development of new drugs. Recent investigations in our laboratory and others identified the PAX8 gene as a major driver of OC, regulating the expression of key genes to promote tumorigenesis. The goal of this proposal is to understand how DNA mutations impact PAX8-dependent control of target gene expression to promote cancer development. The idea is that by understanding pathways upstream of cancer gene expression we can identify much-needed new therapeutic targets for OC.

    Sponsor: Ben Berman, PhD

    Kate Lawrenson, PhD
    Cedars-Sinai Medical Center
  • Development of a Novel dCK Inhibitor for Leukemia and Lymphoma using PET Imaging
    $100,000 Cancer Free Generation Career Development Research Grant

    DI82 is a new potential chemotherapy drug which can kill cancer cells by preventing them from making new DNA. The project will look at drug levels in the blood, tumor, and other parts of the body using an imaging machine (PET). The drug will be tested in mice in combination with two other drugs to determine how well they work together to kill tumor cells. This information will be used in a model to predict how much drug to give patients in future human studies.

    Sponsor: Caius Radu, MD

    Mina Nikanjam, MD, PhD
    University of California, Los Angeles
  • Targeting Myc Oncoproteins in Advanced Prostate Cancer
    $100,000 Irving Feintech Family Foundation Research Grant

    Advanced prostate cancer is a deadly disease with limited treatment options. Two members of the Myc family of cancer genes named c-Myc and N-Myc are active in the main types of lethal prostate cancer – castration-resistant prostate adenocarcinoma and small cell neuroendocrine prostate cancer. In this work, Dr. Lee will clarify the biologic functions of c-Myc and N-Myc in two unique prostate cancer models developed from normal human prostates. Dr. Lee will take advantage of these models of advanced prostate cancer to find new therapies and evaluate a promising inhibitor that directly targets the activity of N-Myc in cancer cells.

    Mentor: Owen N. Witte, MD

    John Kyung Lee, MD
    University of California, Los Angeles
  • Identifying Novel Mechanisms of Immune Evasion in Acute Myeloid Leukemia
    $100,000 Magnolia Council Career Development Research Grant

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and new treatment approaches are urgently needed. Immunotherapy has emerged as a safe and effective treatment for certain solid tumors, however the development of effective immunotherapies for AML requires a better understanding of the mechanisms by which leukemia evades the immune system. AML is associated with selective dysregulation of antigen presenting cells (APCs), which are a vital component of anti-tumor immune responses. The study will investigate mechanisms by which leukemia cells interfere with APC development with the goal of identifying novel immunotherapeutic targets in AML.

    Mentor: Gay M. Crooks, MD

    Christopher Seet, MD, PhD
    University of California, Los Angeles
  • Regulation of PD-L1/L2 Expression in Melanoma
    $100,000 Cancer Free Generation Career Development Research Grant

    The field of immuno-oncology has evolved over the past century, however, its therapeutic application to fight cancer has just begun with recent approval of new immunotherapy drugs in 2014. Anti-PD-1 antibodies produce unprecedented long lasting responses for patients with advanced melanoma and advanced lung cancer, it is expected to be approved for many other cancer types. Dr. Shin will study the regulation of PD-L1/L2 expression in response to interferons which will be highly relevant to understanding the response and resistance from anti-PD-1/L-1 antibody therapy and its great potential to develop an assay or identify bio-markers to predict the response.

    Mentor: Antoni Ribas, MD PhD

    Daniel Sanghoon Shin, MD
    University of California, Los Angeles
  • Double Immune Suppression Blockade to Treat Melanoma
    $100,000 Katz Family Foundation Career Development Research Grant

    The success of tumor immunotherapy for the treatment of melanoma is limited by the presence of intratumoral immune suppressive cells. Our preclinical animal study showed a small molecule inhibitor of key myeloid cell receptor called CSF-1R would cripple the immune suppressive myeloid cells and improve the antitumor activity of effector immune cells. This allowed us to partner with Plexxikon to provide the CSF-1R inhibitor PLX3397 and Merck to provide the anti-PD-1 antibody MK-3475. We propose a phase 1 dose-escalation study to combine these two drugs, in patients with metastatic melanoma. We will do correlative studies to test mechanism of combinatorial effects.

    Mentor: Antoni Ribas, MD, PhD

    Siwen Hu-Leiskovan, MD, PhD
    University of California, Los Angeles
  • Role of the Long Noncoding RNA DANCR in T Cell Acute Lymphoblastic Leukemia
    $100,000 Cancer Free Generation Career Development Research Grant

    T cell leukemia (T-All) is a type of blood cancer that affects children and adults. Newer treatments are urgently needed, as 20% of children and 50% of adults with T-ALL cannot be cured. Our research focuses on a recently discovered gene called DANCR, which is present at abnormally high levels in T leukemia cells. We have found that DANCR promotes the growth of leukemia cells. We are currently studying how DANCR promotes this growth of leukemia cells. These studies could ultimately lead to the development of new anti-DANCR treatments for leukemias.

    Mentor: Alan Wayne, MD

    Chintan Parek, MD
    Children’s Hospital of Los Angeles
  • Hematopoietic Stem Cell and Progenitor Cell Senescence and Therapy Related Acute Myeloid Leukemia
    $100,000 Magnolia Council Career Development Research Grant

    Patients with cancer are frequently treated with chemotherapy and/or radiation therapy. A small subgroup of these patients develops a type of leukemia called Therapy-related Acute Myeloid Leukemia (tAML) as a complication. It is a deadly disease with more than 90% of the patients dying within 5 years. Based on our recent work, we think the chemotherapy exposure to normal blood stem cells causes the stem cell to undergo rapid aging and the aged stem cells turn into cancer. The proposed study is to test this idea and in the process to discover how aging of blood stem cells causes leukemia.

    Mentor: Preet Chaudhar, MD, PhD

    Giridharan Ramsingh, MD
    University of Southern California
  • Molecular and immunologic correlates of responses to anti-CD 19 chimeric antigen receptor T cell therapy
    $100,000 Irving Feintech Family Foundation Career Development Research Grant

    CD 19 is a protein on the surface of B cells and serves as a potential target in advanced non-Hodgkin lymphomas and leukemias. One experimental treatment has been anti-CD 19 chimeric antigen receptor (CAR) T cells, which uses the patient’s T cells to engineer an anti-CD 19 portion to specifically recognize and kill CD 19-expressing cells. A clinical trial using anti-CD 19 CAR T cells will be implemented at UCLA in the summer of 2014. We plan to: 1) initiate a phase I clinical trial using transfer of engineered T cells, and 2) perform laboratory studies to improve upon and understand the mechanisms of this treatment.

    Mentor: John M. Timmerman

    Patricia A. Young, MD
    University of California, Los Angeles

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