TCRF
Funded Research

  • 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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