Abstract Background Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that contributes disproportionately to thyroid cancer–related mortality. Historically, systemic treatment options for advanced MTC were limited due to poor responsiveness to radioactive iodine and conventional chemotherapy. The development of targeted therapies has significantly transformed disease management. Methods This narrative review summarizes current evidence on targeted therapies for advanced MTC, including multikinase inhibitors (MKIs), selective RET inhibitors, and emerging treatment strategies. Literature on efficacy, safety, resistance mechanisms, and novel therapeutic approaches was evaluated. Results First-generation MKIs, including vandetanib and cabozantinib, demonstrated clinical benefit by targeting RET and angiogenic pathways, though off-target toxicities limited tolerability. More recently, selective RET inhibitors, such as selpercatinib and pralsetinib, have shown high response rates and improved safety profiles, establishing them as preferred first-line therapies for RET-mutant MTC. However, pralsetinib’s recent market withdrawal due to regulatory challenges highlights the need for additional options. Emerging therapies, including BOS172738, SY-5007, and peptide receptor radionuclide therapy, show promising early results. Resistance mechanisms, including gatekeeper and solvent front mutations, remain a challenge. Advances in clinical biomarkers and novel approaches, such as CAR-T cell therapy, may further support personalized treatment. Conclusion Targeted therapies have reshaped the management of advanced MTC, with selective RET inhibitors offering improved efficacy and tolerability. Continued research is essential to overcome resistance, expand therapeutic options, and improve patient outcomes.
H. Arain, Azeem Izhar, Rachael Caretti et al.· The Oncologist· 0 citations
BackgroundSmoking is a known carcinogen and its relationship with the development of thyroid cancer (TC) is not well established and prior evidence shows a possible protective relationship. We aim to evaluate the impact of smoking on the development of TC.MethodsThis is a retrospective cohort study of adult patients who were diagnosed with a thyroid nodule(s) between 2005 and 2025. Cohorts were developed based on smoking status. Patients with the diagnosis of multiple endocrine neoplasia syndrome or who had known TC were excluded. Propensity score matching (PSM) was performed. The primary outcome was diagnosis of TC. Hazard ratios (HRs) and 95% confidence intervals were calculated. Cohorts were then divided into subgroups based on sex and racial groups with the same analysis.ResultsThere were 404,811 individuals identified who were smokers and had thyroid nodules. Average age was 60 +/- 15 years, with 69% of the cohort being female and 70% white. TC developed in 3.4% of smokers with nodules compared to 1.2% of nonsmokers (HR = 2.60). Subgroup analysis revealed an increased risk across all sex and racial groups. Female smokers had a HR than males at 2.62. Across racial groups, Black patients had the highest HR at 2.91. All groups had confidence intervals that did not cross one.DiscussionIn this retrospective cohort study, smoking was significantly associated with an increased risk of developing TC. There was an increased risk of developing TC in all groups, and Black patients had the highest HR highlighting an area that warrants further investigation.
Rachael Caretti, Raj Roy, H. Arain et al.· The American surgeon· 0 citations
Current evidence supports that an association exists between select chemical exposures and TC development, but study limitations prevent any direct link to causation.
Rachael Caretti, H. Arain, Herbert Chen· The Oncologist· 0 citations