Dr Tauro on the Role of ULK3 in Multiple Myeloma

Marilena Tauro, PhD, research scientist, postdoctoral fellow, Moffitt Cancer Center, discusses the role for ULK3 in regulating autophagy in multiple myeloma.

At the Moffitt Cancer Center, investigators accessed a database containing patient information, including RNA sequencing, for those with multiple myeloma, Tauro begins. This allowed investigators to examine how an induvial autophagy signature increases from the premalignant stage to later stages of the disease. Particularly, the ULK3 protein can increase with the stage of the disease, and an increase in ULK3 is associated with poorer overall survival, Tauro adds. However, by detecting ULK3 in tissue microarrays, it could be used as a biomarker for patient stage and response to treatment, Tauro expands.

Preclinical research aimed to examine the ablation of ULK3, and it showed that multiple myeloma cells cannot survive without it, Tauro explains. Through further collaboration, investigators identified compounds that could inhibit these enzymes. Mouse models were also utilized to investigate different compounds and understand if selected combinations of therapies could benefit patients with increased ULK3, Tauro emphasizes. Mouse models demonstrated an increased overall survival and reduced tumor burden, Tauro continues.

Additionally, the Ex vivo Mathematical Myeloma Advisor (EMMA) platform allowed clinicians to test the combinations directly on patient samples. Cancer cells from patients were cultured with their microenvironment in order to understand how patients would respond to treatment without exposing them to unknown toxicity, Tauro notes. This approach could help screen patients to better understand which population could benefit from this treatment, Tauro concludes.