TY - JOUR
T1 - Review article
T2 - new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance
AU - Hamidi, Sarah
AU - Hofmann, Marie Claude
AU - Iyer, Priyanka C.
AU - Cabanillas, Maria E.
AU - Hu, Mimi I.
AU - Busaidy, Naifa L.
AU - Dadu, Ramona
N1 - Publisher Copyright:
Copyright © 2023 Hamidi, Hofmann, Iyer, Cabanillas, Hu, Busaidy and Dadu.
PY - 2023
Y1 - 2023
N2 - The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.
AB - The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.
KW - drug resistance
KW - immunotherapy
KW - metastatic thyroid cancer
KW - neoadjuvant
KW - novel treatments
KW - radioiodine refractoriness
KW - tyrosine kinase inhibitor
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U2 - 10.3389/fendo.2023.1176731
DO - 10.3389/fendo.2023.1176731
M3 - Review article
C2 - 37435488
AN - SCOPUS:85164597695
SN - 1664-2392
VL - 14
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 1176731
ER -