Precision oncology with selective RET inhibitor selpercatinib in RET-rearranged cancers - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/37360768/
Rearranged during transfection ( RET ) is a protooncogene that encodes for receptor tyrosine kinase with downstream effects on multiple cellular pathways. Activating RET alterations can occur and lead to uncontrolled cellular proliferation as a hallmark of cancer development. Oncogenic ...
Conclusion: Selpercatinib has led to a paradigm change in the management of RET fusion-positive solid tumors including NSCLC and thyroid cancer. Its current tissue-agnostic approval highlights the potential it has in different tumor types. Multiple studies are ongoing with the aim of exploring selpercatinib use in other disease settings and different patients’ populations.
• Source: Therapeutic Advances in Medical Oncology
• Conclusion: “Selpercatinib has led to a paradigm change in the management of RET fusion-positive solid tumors including NSCLC and thyroid cancer. Its current tissue-agnostic approval highlights the potential it has in different tumor types. Multiple studies are ongoing with the aim of exploring selpercatinib use in other disease settings and different patients’ populations.”
• Selpercatinib is a selective small molecule inhibitor of RET kinase that works by an ATP competitive mechanism, with high selective potency vs. RET fusions and mutations.
• Acquired resistance by multiple mechanisms is cropping up with selpercatinib. Strategies to overcome this resistance include combination with other targeted agents (e.g., crizotinib), as well as the use of second-generation drugs, which are in early-phase trials. These new drugs could delay the emergence of mutations and lengthen PFS.
• Various ongoing studies are assessing expanded indications for selpercatinib in RET fusion-positive cancers. In LIBRETTO-432, for instance, selpercatinib is being tested in an adjuvant setting vs. placebo in patients with early-stage NSCLC following curative intent surgery or radiation therapy. It is also being investigated in the neoadjuvant setting, with preoperative selpercatinib being administered to patients with thyroid cancer or RET alterations