COLUMBUS, Ohio – Researchers from The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) have been awarded a five-year, $2.1 million grant from the National Cancer Institute to study new combination radiation and targeted medical therapy approaches for thyroid cancer.  Co-led by Terence Williams, MD, PhD, and Manisha Shah, MD, this new grant will enable a multidisciplinary cancer research team at the OSUCCC – James to evaluate how BRAF gene mutations promote therapeutic resistance to radiation and other genotoxic therapies in patients with anaplastic thyroid cancer (ATC). This rare and aggressive form of thyroid cancer represents 1-2% of all thyroid cancer diagnoses. The investigators say they expect this new research to help develop tumor-selective approaches to enhancing sensitivity to genotoxic therapies for BRAF-mutant and BRAF wild-type ATC, potentially improving physicians’ ability to treat and control the disease. Previous studies have shown that BRAF-activating mutations are the most common oncogenic mutations in ATC, occurring in 30-40% of tumors. “Our preliminary data supports that BRAF mutations promote therapeutic resistance to radiation and other genotoxic therapies” for ATC, such as external beam radiation therapy (EBRT) and cytotoxic chemotherapy, says Williams, principal investigator of the grant and a radiation oncologist at the OSUCCC – James.  “Our patients with ATC face high rates of recurrence, and it is particularly difficult because advanced disease can impact patients’ ability to breathe and eat. More effective medical therapies are urgently needed to improve disease control and lengthen survival,” says Shah, co-principal investigator of the grant and a medical oncologist at the OSUCCC – James. “This new grant represents an exciting opportunity to explore ways to improve radiation sensitivity and chemotherapy for multiple subtypes of BRAF-mutant and BRAF wild-type ATC.”  The OSUCCC – James team will conduct a phase I clinical trial to determine the maximum tolerated doses of the drugs dabrafenib (a BRAF gene inhibitor) and trametinib (a MEK-1/2 gene inhibitor) to be used concurrently with external beam radiation therapy in patients with BRAF-mutant ATC. The team will then identify biomarkers of response and molecular pathways leading to resistance.  This investigator-initiated clinical trial led by Shah has been recently opened to patient accrual at the OSUCCC – James. The trial is expected to open at other national leading cancer centers, including MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center. Up to 24 patients nationwide will be recruited to this study.  Researchers will also conduct laboratory studies aimed at better understanding how BRAF-mutant ATC leads to accelerated DNA repair, test novel therapeutic strategies that target components of DNA repair, and develop and optimize strategies for targeting DNA repair in combination with EBRT and other genotoxic therapies for BRAF-mutant ATC. Previous studies funded by an NCI Thyroid Specialized Program of Research Excellence (SPORE) grant (PI: Matthew Ringel, MD) and a Pelotonia Idea Grant provided data that helped pave the way for this new NCI grant. Ringel is also a co-investigator on these new studies. To learn more about thyroid research and patient care at the OSUCCC – James, visit cancer.osu.edu/thyroid or call 1-800-293-5066. -30- Media Contact: Amanda J. Harper OSUCCC – James Media Relations Direct Line: 614-685-5420 Central Media Relations: 614-293-3737 Amanda.Harper2@osumc.edu