TCRF
Funded Research

  • Novel Drug Targets for High Grade Serous Ovarian Cancer identified through Induced Pluripotent Stem Cell Modeling of Disease
    $500,000 Tower Senior Investigator Grant

    Faults in high risk genes cause high grade serous ovarian cancer (HGSOC). This cancer is often lethal in patients. Novel drugs are needed to improve treatment and patient outcomes. We plan to use cells from individuals carrying high risk genes to develop precision models of their disease and then cutting edge methods in genomics and functional screens to identify novel therapeutic targets that can be tested for their potential to treat patients with HGSOC. Ultimately we expected these studies will improve survival rates in patients that get HGSOC because they carry faulty genes.

    Simon Gayther, PhD
    Cedars-Sinai Medical Center
  • The impact of alpha catenin loss on DNA repair defects in triple negative breast cancer
    $500.000 Barry Rosenbloom, MD Senior Investigator Grant

    Triple negative breast cancer (TNBC) is an aggressive and has a high death rate, especially in black women. We have found a gene marker that may make these tumors escape chemotherapy. Our research also shows that when this marker is not present, the tumor cells respond to a very specific type of cancer therapy. Also, there might be more immune cells that come into the tumor. Therefore, we wish to expand our research help better understand the role of this marker in breast cancer growth to improve treatment of this hard to treat form of cancer.

    John Carpten, PhD
    University of Southern California
  • Targeting Monoamine Oxidase A to Expand Cancer Immune Checkpoint Blockade Therapy
    $500,000 Magnolia Council Senior Investigator Grant

    Immune checkpoint blockade (ICB) therapies have revolutionized the treatment of many cancers; however, the existing ICB therapies can only benefit a small fraction of cancer patients, demanding an expansion of ICB therapies. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MOIs) have been developed and are clinically used for treating depression. This proposal aims to study MAO-A regulation of antitumor immunity and evaluate MAO-A blockade for cancer immunotherapy. The project has the potential to identify MAO-A as a new immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.

    Lili Yang, PhD
    University of California, Los Angeles
  • Polo-like Kinase 4 as a Regulator of Cytokinesis and as a Target for Cancer Therapy
    $500,00 Jessica M. Berman Memorial Fund Senior Investigator Grant

    Polo-like kinase 4 (PLK4) regulates duplication of each cell’s centrosome, which facilitates movement of duplicated chromosomes to opposite poles in dividing cells. Without two centrosomes cells cannot divide; hence preventing cancer cell duplication. We have also found that PLK4 controls a final step in cell division, known as cytokinesis. We are part of a research collaboration that has developed a new drug, CFI-400945, which inhibits PLK4 activity. Our proposal seeks support to identify biomarkers that predict which cancers cannot complete cell division when PLK4 function is inhibited and which cancers, like normal cells, can complete cell division.

    Michael F. Press, MD, PhD
    University of Southern California
  • Targeting Mismatch Repair System for Cancer Therapy
    $500.000 Magnolia Council Senior Investigator Grant

    Despite decades of extensive studies in cancer research, cancer is still the number 2 leading cause of death in the United States. The major problem is that individual cancers display distinct genetic abnormalities, and none of the known treatments and their combination can effectively deal with these abnormalities. We have recently created a mutant DNA repair protein that irreversibly binds to cancer cell-specific DNA errors during cancer growth, leading to cell death. This application aims to develop this mutant DNA repair protein into an effective drug for cancer therapy.

    Xiaojiang Chen, PhD
    University of Southern California
  • Next-Generation Estrogen Receptor Downregulators for Breast Cancer Therapy
    $500,000 Jessica M. Berman Memorial Fund Senior Investigator Grant

    Despite remarkable improvements in treatment options, development of endocrine resistance is one reason that breast cancer is the second most frequent cause of cancer death in women. In most cases, estrogen receptor (ER) is present in these resistant tumors, and in many ER continues to regulate tumor growth. This project aims to develop a new clinical-translational strategy to address this challenge and promote patient survival. Dr. Pietras plans to develop a new generation of selective ER downregulators (termed SERDs) with the proper biologic/pharmacologic profile to be used as therapeutics for endocrine-sensitive and -resistant cancers in clinic.

    Richard J. Pietras, MD, PhD
    University of California, Los Angeles
  • Synthetic Lethal Drug Discovery In Triple Negative Breast Cancer
    $500,000 Michele and Ted Kaplan Family Senior Investigator Grant

    PARP inhibitors are promising new drugs for a subset of breast and ovarian cancers. However, as single agents PARP inhibitors show little activity in triple-negative breast cancer (TNBC). Dr. Koefler will use a TNBC cell model to evaluate the effect of single gene mutations on the response to PARP inhibition. Mutations conferring sensitivity will be further tested in cell lines, animal models, and TNBC patients. Based on our findings, Dr. Koefler will develop an assay to evaluate PARP sensitivity in clinical samples. The study will provide valuable insights that can be translated into biomarkers for patient selection, and new drug combination therapies.

    Phillip Koeffler, MD
    Cedars-Sinai Medical Center

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