Redifferentiating Thyroid Cancer: Selumetinib-enhanced Radioiodine Uptake in Thyroid Cancer

In a recent article, we reported a restorative therapeutic intervention that turned individual thyroid cancer lesions into more efficient tissues for taking up radioactive iodine (RAI), resulting in clinically significant and durable responses. A group of Iodine-131 refractory thyroid cancer patients were treated with the MEK tyrosine kinase inhibitor (TKI) selumetinib, and RAI uptake was restored in a subset of patients. We employed Iodine-124 positron emission tomography to measure radiation absorbed dose, on a lesion by lesion basis. The process can be thought of as a re-differentiation of the cancer toward a more nearly normal state most like the tissue from which the cancer arose. Remarkably, in its own way, a change was detected within a few weeks of treatment, restoring uptake with therapeutically effective levels of RAI and in some patients, previously completely refractory to radioiodine treatment. In this article, we summarize the basic work that led to this seminal study, and make the case for lesional dosimetry in thyroid cancer with Iodine-124 as a new optimal radiotracer for precision medicine in patients with well differentiated thyroid cancer.