Systemic Therapy for Advanced Thyroid Cancer-New Personalized Options.

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Advanced thyroid cancers (RR-DTC, ATC, MTC) show poor response to traditional chemotherapy.
• Tyrosine kinase inhibitors (TKIs) represent a paradigm shift in systemic therapy for these aggressive malignancies.
• Personalized medicine, driven by genomic profiling, is increasingly central to thyroid cancer treatment.

Purpose of the Study:

• To review current evidence on the efficacy and safety of drug therapies for advanced thyroid cancers.
• To explore the role of personalized, targeted therapies in managing these diseases.
• To highlight the impact of molecular testing and next-generation sequencing in tailoring treatment.

Main Methods:

• Review of contemporary evidence on drug therapies for thyroid cancers.
• Analysis of clinical trial data for multikinase inhibitors (MKIs) and targeted therapies.
• Examination of the integration of molecular testing (e.g., next-generation sequencing) in treatment decisions.

Main Results:

• Multikinase inhibitors (sorafenib, lenvatinib, vandetanib, cabozantinib) improve progression-free survival and response rates in RR-DTC and MTC.
• BRAF-directed therapies show efficacy in anaplastic thyroid cancer with BRAF V600E mutations, enhancing survival.
• Highly-selective inhibitors targeting RET, NTRK, and other alterations refine treatment based on tumor genetics.

Conclusions:

• TKIs and targeted therapies have revolutionized advanced thyroid cancer treatment, offering improved outcomes.
• Molecular testing is crucial for personalized treatment selection, tailoring therapies to individual tumor profiles.
• Challenges remain, including drug resistance, toxicity, and equitable access to molecular diagnostics and targeted treatments, necessitating further research.