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Join us as City of Hope Researcher Dr. Linda Malkas speaks about “Mechanistic Study of the Superior Anti-Cancer Properties of a First-in-Class Small Molecule Targeting PCNA”
Date: Friday, February 21, 2020, at 12:00 p.m.
Location: Building 121, Classroom 1110
Abstract: Proliferating cell nuclear antigen (PCNA) plays a central role in maintaining genome integrity and is indispensable to the growth and survival of cancer cells. To overcome the challenges associated with inhibiting an essential protein, we sought small molecules that target the cancer- distinct L126-Y133 region of PCNA. Here, we report the superior therapeutic properties and mechanism of action of a PCNA inhibitor (AOH1996), which preferentially inhibits the loading of PCNA and the recruitment of MCM7 to actively transcribed chromatin regions without affecting their presence at heterochromatin. The compound selectively kills cancer cells but is not associated with significant toxicity to non-malignant cells. It enhances replication stress in cancer cells and works synergistically with DNA damaging chemotherapeutic drugs to induce cancer cell death. Orally administrable in mice and dogs, AOH1996 suppresses tumor growth in a dosage form compatible with clinical applications and causes no significant toxicity at 2.5 times its effective dose.
Snacks will be provided. Please feel free to bring your lunch to eat during the seminar.