The Efficacy and Safety of RET-selective Inhibitors for Cancer Patients

Abstract

The rearrangement during transfection (RET) encodes a receptor tyrosine kinase (RTK), which is involved in the development of various tissues and cells. The rearrangements and mutations of RET contribute to the development of a variety of human malignancies. Therefore, RET alterations are novel therapeutic targets. Inhibitors for RET and other kinases have been approved for the treatment of RET-altered tumors and have demonstrated their benefits for some types of cancer patients in clinics. However, due to off-target effects, these inhibitors have some adverse effects and dose-limiting toxicity. Therefore, long-term treatment with these inhibitors has potential limitations. Novel highly selective inhibitors (pralsetinib and selpercatinib) that target the RET pathway are well tolerated and have significant and long-lasting antitumor activity. They have been accelerated for approval by the FDA. This article will focus on the role of highly selective inhibitors targeting the RET and their efficacy and safety in therapy for RET-associated cancers.