The rate of new thyroid cancer cases in the U.S. has steadily declined over the last decade, largely due to stricter criteria for diagnosing the disease despite increased detection. However, the mortality rate for people in Wisconsin remains higher than the national average, signaling a need for more effective therapies. MCW cancer scientists are committed to making this a reality, exploring targeted treatments for patients with a specific type of thyroid cancer that has a mutated RET (Rearranged during Transfection) gene. In a new study, investigators discovered that a novel combination of two drugs, selpercatinib and MitoQ, was powerful in killing thyroid cancer cells with RET mutations, and resulted in fewer adverse effects than existing therapeutic approaches. These results, published in NPJ Precision Oncology, open the door to treatment options that are more tolerable for patients and could improve their quality of life.
“RET is a gene that encodes a receptor tyrosine kinase, a protein involved in cell growth and communication. When RET is altered or mutated, it can cause cells to grow uncontrollably and lead to the development of various cancers. While advanced drugs that can directly target RET have been approved to treat RET-mutant thyroid cancer, there are patients who cannot tolerate these therapies. This combination treatment brings a new hope to patients who struggle with adverse effects from existing medicines,” said Jong-In Park, PhD, professor of biochemistry and study co-author.
“The combination of selpercatinib—a precision medicine that targets mutated RET more directly than previous drugs—and a dietary supplement called MitoQ effectively suppress RET-mutated thyroid tumor cells by inducing a synergistic effect. This combination has shown promising results in both preclinical models and in a clinical context with patients who could not tolerate full doses of selpercatinib,” added Dr. Park.
After testing the combination therapy in mice, the research team evaluated its effects in two patients with RET-mutant thyroid cancer who were unable to take selpercatinib at regular doses due to having adverse effects. Both patients showed tumor reduction, and the quality of life of one patient significantly improved over a year until the tumor relapsed. Dr. Park explained that tumors eventually develop resistance to RET inhibitors, and that scientists are working hard to understand how drug resistance affects the mitochondrial sensitivity of tumor cells. The team will explore these mechanisms in the next phase of their research, in addition to testing different drug combinations that can target tumor cell mitochondria.
“MitoQ has proven to be safe in humans, and its clinical benefits are currently being evaluated in phase 2 clinical trials, although its benefit for cancer patients has not yet been tested in the setting of a clinical trial. Our preclinical data and patient cases are pertinent to the design of future trials to determine whether this novel combination can provide a clinical benefit to patients with RET-mutated cancers,” said Dr. Park.
Read the full study in NPJ Precision Oncology.