Selpercatinib is a selective RET kinase inhibitor. RET stands for rearranged during transfection and refers to a receptor tyrosine kinase involved in cellular signaling.
In certain cancers, genetic alterations involving RET can produce abnormal signaling that promotes cell growth and survival. These alterations can occur as gene fusions or activating mutations, depending on the cancer.
Simple explanation
A useful way to understand selpercatinib is to think of RET as a molecular signaling pathway. When a cancer-driving RET alteration keeps that pathway abnormally active, tumor cells may receive signals that support continued growth.
Selpercatinib binds to RET kinase and inhibits its activity. By reducing RET signaling, it can interfere with a molecular driver of certain RET-positive cancers.
RET fusions
RET gene fusions can occur in cancers such as certain non-small cell lung cancers and thyroid cancers. In a fusion, part of the RET gene becomes joined with another gene, producing an abnormal protein with signaling activity.
For RET fusion-positive cancers, identifying the alteration through an appropriate molecular test is central to treatment selection.
RET mutations
RET mutations are particularly important in medullary thyroid cancer. Some mutations can activate RET signaling and contribute to tumor development and progression.
The current U.S. indication for medullary thyroid cancer specifically requires a RET mutation detected by an FDA-approved test.
Selective rather than broadly multi-targeted
Selpercatinib was developed as a selective RET inhibitor rather than as a conventional nonspecific cytotoxic chemotherapy. Its therapeutic rationale is therefore closely tied to the molecular biology of RET-driven disease.
Central nervous system activity
Clinical development has included evaluation of patients with brain metastases and CNS disease. The clinical program has reported intracranial activity in selected RET-driven cancers, although individual outcomes vary and clinical decisions require the applicable evidence and patient-specific assessment.