Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Medullary thyroid carcinoma (MTC) is a rare thyroid cancer originating from C cells, occurring sporadically or as part of MEN 2 syndrome.
• Hereditary MTC is linked to germline RET proto-oncogene mutations, while sporadic forms involve somatic RET or RAS mutations.
• Early surgical intervention is crucial for MTC cure, and RET genetic screening has improved outcomes for hereditary cases.

Purpose of the Study:

• To review current understanding of MTC pathogenesis and intracellular signaling pathways.
• To discuss therapeutic approaches and challenges in managing advanced MTC.
• To highlight the potential of targeted molecular therapies for MTC treatment.

Main Methods:

• Review of existing literature on MTC pathogenesis, genetics, and treatment.
• Analysis of current therapeutic strategies, including multikinase inhibitors (MKIs).
• Focus on the development and potential of next-generation small-molecule tyrosine kinase inhibitors (TKIs).

Main Results:

• Current MKIs (vandetanib, cabozantinib) improve progression-free survival but not overall survival in advanced MTC.
• Nonselective MKIs can cause significant off-target toxicities, limiting efficacy.
• Next-generation TKIs offer potent and selective targeting of oncogenic RET alterations.

Conclusions:

• Advanced MTC management remains challenging despite recent therapeutic advances.
• Next-generation TKIs represent a promising therapeutic strategy for advanced MTC due to their targeted approach.
• Further research into selective molecular therapies is crucial for improving overall survival in MTC patients.