Timeframe: 2025 – 2027
Goal: Investigate ways to therapeutically target DNAJ-PKAc
Principal Investigators: John Gordan, MD, PhD
Study overview: Testing drugs in cells and living organisms is a critical step in developing new treatments. For a drug to work, it must move through complex cell structures and, in animals and eventually humans, overcome challenges like absorption, distribution, metabolism, and excretion (often called ADME). Studying how these drugs behave in cells and in animal models not only shows whether they work but also helps us understand which cancer pathways they affect. This knowledge can guide combination therapies and predict which patients might respond—or develop resistance.
This is especially important for Fibrolamellar Carcinoma (FLC), where the cancer-driving kinase DNAJ-PKAc operates as part of a larger protein complex. Its partners may influence how drugs bind and work, so these interactions need to be studied carefully.
This effort is led by Dr. John Gordan, a physician-scientist with deep experience in cancer drug development. His team will create specialized cell models that can tell the difference between the DNAJ-PKAc fusion protein and its normal counterpart. This is essential for designing drugs that target only the cancer-driving fusion. They will also test promising compounds in animal models to move candidate drugs closer to treatments for patients.