The Repotrectinib

In the past 2 decades, the understanding of cancer pathogenesis at the molecular level has helped therapy-targeting specific oncogenic drivers to be an outstanding factor in cancer therapy. Receptor tyrosine kinases consist of a wide family of cell surface receptors that play an important role in the regulation of cellular processes. These processes include the progression of many types of cancers that are targeted by several tyrosine kinase inhibitors (TKIs). However, gatekeeper mutations and solvent front mutations show resistance to current TKIs, such as ceritinib, ensartinib and larotrectinib. Repotrectinib is a new generation of TKI that is potent for anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1) and neurotrophic tropomyosin receptor kinase (NTRK) rearrangement cancers, including wild-type and gatekeeper/solvent front mutations. Although data is limited since it is a new drug, current reports show its potency in most known mutation typessuch asALK(G1202R), ROS1(G2032R), ROS1(D2033N),TRKA(F589L),TRKBF623L and TRKCF617I. In this review, the characteristics of repotrectinib and its in vitro and in vivo studies in comparison with other ALK/ROS1 and TRK inhibitors are detailed along with the descriptions of phase I/II clinical trials of repotrectinib.