Precision oncology with selective RET inhibitor selpercatinib in RET-rearranged cancers

Area of Science:

• Oncology
• Molecular Biology
• Precision Medicine

Background:

• Rearranged during transfection (RET) is a protooncogene encoding a receptor tyrosine kinase.
• Activating RET alterations, including fusions and mutations, drive uncontrolled cellular proliferation in various cancers.
• RET alterations are implicated in non-small cell lung cancer (NSCLC), thyroid cancer, and other malignancies.

Purpose of the Study:

• To review the current status of selpercatinib, a selective RET inhibitor.
• To discuss the efficacy of selpercatinib in RET fusion-positive NSCLC and thyroid cancers.
• To highlight the tissue-agnostic activity and FDA approval of selpercatinib.

Main Methods:

• Review of clinical trials and literature on RET inhibitors.
• Analysis of data regarding the prevalence of RET alterations in different cancer types.
• Evaluation of selpercatinib's clinical outcomes and FDA approvals.

Main Results:

• Oncogenic RET fusions occur in approximately 2% of NSCLC and 10-20% of thyroid cancers.
• RET mutations are key drivers in sporadic and hereditary medullary thyroid cancers.
• Selpercatinib has demonstrated significant efficacy and received FDA approval for RET-altered tumors, including tissue-agnostic indications.

Conclusions:

• Selective RET inhibitors, such as selpercatinib, represent a significant advancement in precision oncology.
• Selpercatinib offers a targeted therapeutic option for patients with RET fusion-positive NSCLC, thyroid cancers, and other RET-altered malignancies.
• The success of selpercatinib underscores the importance of identifying RET alterations for guiding cancer treatment.