Targeting ATP13A3 for neuroblastoma therapy

Combination therapy of targeting polyamine synthesis (with DFMO) and cellular uptake has been successful in pre-clinical neuroblastoma models, and is currently being tested in phase I clinical trials. Our team identified a role for the polyamine transporter ATP13A3 in neuroblastoma. ATP13A3 is linked to worse outcome in patients, whereas other preliminary evidence flags ATP13A3 as the main transporter impacting polyamine uptake and neuroblastoma proliferation. We therefore, propose that targeting ATP13A3 represents a selective therapeutic approach. Via high-throughput screening and rational design we will identify hits that selectively block ATP13A3. Complementary, we will design toxic polyamine analogs that are selectively taken up by ATP13A3-expressing tumor cells. Our project will offer partnership and licensing opportunities with industry, and may be extended to other difficult-to-treat cancer types relying on ATP13A3, such as pancreatic cancer.