Previously Funded Research

Timothy Martin, PhD

University of Virginia School of Medicine, Charlottesville

Research Project:

Defining how UFMylation pathway inhibition enhances anti-lung tumor immunity

Summary:

The body’s naturally protective immune system can recognize cancer cells as something abnormal and destroy them before they get a chance to form a tumor. However, as tumors grow, cancer cells evolve strategies that keep them alive even when faced with the very immune cells capable of killing them. Recent therapeutic advances in restoring effective tumor killing by the immune system include the immunotherapies that are used clinically to treat a variety of tumor types including lung cancer.

Unfortunately, the success of immunotherapies in lung cancer has been limited to certain patient populations. Lung squamous cell carcinoma (LUSC) is particularly non-responsive to immunotherapies. Identifying new, effective strategies to bring these breakthrough treatments to the larger population of lung cancer patients is direly needed.

In recent studies, we uncovered cancer drug targets whose inhibition helps promote tumor destruction by the immune system. One of these candidate therapeutic targets, UBA5, will be investigated in detail using mouse models of lung cancer and with two pre-clinical UBA5 inhibitors. We will determine if inhibiting UBA5 effectively reduces lung tumor growth and identify whether combining UBA5 inhibition with FDA-approved immunotherapies leads to a more effective immune response particularly in non-responsive LUSC tumors. These studies aim to bring life-saving immunotherapies to the currently large, non-responsive lung cancer patient population.