2023

Exploiting a Critical Vulnerability to Glutamine Antimetabolite Therapy in Fibrolamellar Hepatocellular Carcinoma (FLC)

Timeframe: 2023 – 2028 Goals: Assess the potential of an inhibitor of glutamine metabolism (DRP-104; sirpiglenastat) in combination with an immune checkpoint inhibitor (durvalumab) as a treatment option for unresectable disease Principal Investigators: Marina Baretti, MD and Mark Yarchoan, MD Study overview: This phase Ib/2 clinical study, led by Dr. Marina Baretti and Dr. Mark …

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CRISPR-engineering of human liver organoids to study fibrolamellar carcinoma

Timeframe: 2023 – 2025 Goals: Model development and understanding the requirements for FLC tumor formation Principal Investigators: Benedetta Artegiani, PhD; and Delilah Hendriks, PhD Study overview: In comparison with more common cancers, research models of FLC have been extremely limited. Drs. Artegiani and Hendriks have addressed this problem by creating “synthetic” models of FLC, generating …

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Development and Characterization of Patient-derived Models of Fibrolamellar Carcinoma

Timeframe: 2023 – 2025 Goal: Evaluate selective inhibitors of polo-like kinase 1 (PLK1) for effectiveness in human models of FLC Principal Investigator: Taran Gujral, PhD Study overview: Abormal cell signaling by the DNAJ-PKAc fusion protein kinase drives the uncontrolled growth of fibrolamellar carcinoma. Thus far, however, drugs that inhibit the fusion kinase also block the …

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Therapeutic modulation of tumor-infiltrating T cell function in fibrolamellar carcinoma

Timeframe: 2023 – 2025 Goals: Identifying factors in the tumor environment that impair immune responses to FLC and defining potentially effective immunotherapy strategies Principal Investigators: Venu Pillarisetty, MD (University of Washington); and Kevin Barry, PhD (Fred Hutchinson Cancer Center) Study overview: Immunotherapy – harnessing patients’ immune systems to attack tumor cells – has become established …

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