New Target for Small Cell Lung Cancer

Researchers in the Jacks and Vander Heiden labs identified a new therapeutic target for small cell lung cancer (SCLC), an especially aggressive form of lung cancer with limited options for treatment. In a study appearing in Science Translational Medicine and featured in the NIH Director's Blog, the team used genetic screens to search for SCLC targets that could be tested relatively quickly and easily in a clinical setting. Researchers discovered a metabolic vulnerability to the loss of DHODH, a key enzyme in the pyrimidine synthesis pathway. They also found that a DHODH inhibitor brequinar—already approved for use in patients as an immunosuppressant—slowed tumor progression and increased survival in SCLC mouse models and was effective in treating two of four patient-derived small cell lung cancer tumor models. The study was funded in part by the MIT Center for Precision Cancer Medicine.