A group of investigators in the Endocrine Neoplasia Research Laboratory at Vanderbilt University Medical Center has received national recognition for their work to discover better treatments for thyroid cancer.
A paper describing their lab work was awarded first place in the Basic Science category at the 2021 Cancer Research Competition, which promotes the achievements of oncologic physicians in training. The annual competition is hosted by the American College of Surgeons Commission on Cancer and the American Cancer Society.
David Hanna, MD, a surgical resident at VUMC, presented the paper “RSL3 Induces Ferroptosis via GPX4 Inhibition in Papillary Thyroid Cancer.” He was one of two first-place winners in the category. The research was published in the Journal of American College of Surgeons after the Commission on Cancer Plenary Session on Oct. 20.
The research team is led by Naira Baregamian, MD, assistant professor of Surgery in the Division of Surgical Oncology and Endocrine Surgery. Other team members include Sekhar Konjeti, PhD, staff scientist, and Sriram Cyr, medical student. Baregamian’s research lab focuses on metastatic papillary thyroid carcinomas, more specifically the metabolic rewiring of tumor microenvironment that drives tumor aggressiveness.
Baregamian and Konjeti recently demonstrated that papillary thyroid carcinomas are rich in antioxidants, such as glutathione, and that tumors that recur show higher glutathione accumulation within the tumor microenvironment.
They sought to target tumor molecular pathways that are dependent on glutathione and its metabolism to foil tumor progression.
They found that a small molecule drug, RSL3, inhibits an enzyme called glutathione peroxidase 4 (GPX4), which is overexpressed in papillary thyroid carcinoma specimens and prevents ferroptosis, a form of programmed cell death.
They also found that RSL3 suppresses a critical mTOR pathway and its downstream signaling proteins. The RSL3 treatment effect led to increased DNA damage and incapacitated the DNA damage repair responses within thyroid tumor cells.
The research team is continuing its work to discover methods to dismantle the antioxidant shield of thyroid cancers so ferroptosis can be activated in their quest to offer a novel therapeutic target in patients with aggressive recurrent thyroid cancers.
This Vanderbilt research project by Baregamian’s lab is supported by a Burroughs Wellcome Fund VUMC SCRIPS faculty scholar award and a Vanderbilt-Ingram Cancer Center grant funded by its Cancer Center Support Grant from the National Cancer Institute.