Abstract
For differentiated thyroid cancer (DTC), systemic therapy with radioactive iodine (RAI) is utilized for radiosensitive disease, while for radioiodine refractory (RAIR) disease, current standard of care is treatment with multikinase tyrosine kinase inhibitors (TKI). For BRAF-mutant DTC or anaplastic thyroid cancer (ATC), treatment with inhibitors targeting BRAF and MEK are important advances. RET-inhibitors for RET-mutated medullary thyroid cancer (MTC) recently have been FDA-approved for metastatic disease. Nevertheless, treatment of thyroid cancer resistant to current systemic therapies remains an important area of need. Resistance mechanisms are being elucidated, and novel therapies including combinations of BRAF and MEK inhibitors with RAI or other targeted therapies or TKIs combined with checkpoint inhibition are current areas of exploration.
Highlights
The incidence of thyroid cancer (TC) in the United States is rapidly increasing, with over 52,000 new patients diagnosed and greater than 2,000 deaths recorded each year [1]
While 45% of patients with metastatic differentiated thyroid cancer (DTC) are alive at ten years [2], only 20% of patients with medullary thyroid cancer (MTC) are living at 10 years
Cytotoxic chemotherapy such as adriamycin has limited utility for metastatic TC [4]; in contrast, targeted agents are the mainstay of standard therapy, building on the knowledge that aberrant signaling of the MAPK and PI3K/Akt/mTOR pathways are responsible for tumorigenesis [5]
Summary
The incidence of thyroid cancer (TC) in the United States is rapidly increasing, with over 52,000 new patients diagnosed and greater than 2,000 deaths recorded each year [1]. The National Comprehensive Cancer Network (NCCN) guidelines recommend considering other systemic therapies for progressive, disseminated disease and/or symptomatic disease that is refractory to RAI. Cytotoxic chemotherapy such as adriamycin has limited utility for metastatic TC [4]; in contrast, targeted agents are the mainstay of standard therapy, building on the knowledge that aberrant signaling of the MAPK and PI3K/Akt/mTOR pathways are responsible for tumorigenesis [5]. Mechanisms of resistance and strategies to overcome treatment resistance are areas of active investigation
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