[RET Gene Alterations in Thyroid Cancer-Towards Treatment with Selective RET Inhibitors]

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Context:

• The Rearranged during transfection (RET) gene, encoding a receptor tyrosine kinase, is a key driver in thyroid cancer.
• Genomic alterations in RET, including fusions and mutations, lead to constitutive activation of downstream signaling pathways, promoting oncogenesis.
• These alterations are prevalent in both papillary and medullary thyroid cancer subtypes.

Purpose:

• To summarize the role of RET gene alterations in thyroid cancer pathogenesis.
• To highlight the significance of RET alterations in driving cancer development.
• To underscore the importance of detecting RET alterations for therapeutic strategies.

Summary:

• Two main types of genomic alterations in the RET gene are observed in thyroid cancer: fusions with partner genes in papillary thyroid cancer and mutations in hereditary and sporadic medullary thyroid cancers.
• These alterations result in the constant activation of downstream signaling pathways, contributing to cancer formation.
• Selective RET inhibitors have been developed and approved for treating RET-altered thyroid and lung cancers.

Impact:

• The development of targeted therapies, such as selective RET inhibitors, offers new treatment avenues for patients with RET-altered thyroid cancer.
• The identification of RET as a driver gene emphasizes the need for precise diagnostic methods, including companion diagnostics, for effective patient management.
• Future clinical practice will likely involve routine detection of genomic alterations in the RET gene to guide treatment decisions.