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Active ingredient of the month: entrectinib
by Karin Hollricher (Laborjournal-Issue 1-2, 2021)
(February 8th, 2021) Last year 32 drugs were newly approved in the EU, 13 of which received orphan drug status for the treatment of rare diseases. Among them was the active ingredient entrectinib developed by Ignyta (USA). After taking over Ignyta, Roche now markets the cancer drug under the brand name Rozlytrek.
Entrectinib inhibits three tropomyosin receptor kinases (TRK) from genes NTRK1, 2 and 3 be coded. These kinases influence the development of neurons. They are located in the cell membrane, are involved in signal transmission and can control cell division and differentiation.
NTRKGenes can become oncogenes: if they are incorrectly linked to another gene, they trigger the development of tumors - often by activating the MAPK signaling pathway. The most common gene fusion found in humans is a translocation of NTRK3 on chromosome 15 to the gene ETV6 on chromosome 12. ETV6 is a transcription factor that is necessary for the development of cells in the blood system.
TRK fusion tumors are not limited to one cell type; they are found in many types of cancer. With single-digit percentages, they are much rarer in adults than in children; NTRK-Gender mergers triggered.
Three years ago, small molecules that inhibit these NTR kinases were tested for the first time with positive results. Further studies showed success in the treatment of a wide variety of cancers, in which NTRKGene fusions had been detected. These inhibitors are particularly effective in children with fibrosarcoma, and remissions have even been achieved.
In 2019, Bayer approved larotrectinib, the first NTRK inhibitor, and in 2020, the second of its kind with entrectinib - for the treatment of all tumors in whose cells a molecular diagnosis NTRK-Fusion can demonstrate. In addition, it can be used to treat ROS1-positive, non-small cell lung carcinomas in which the gene ROS1, which codes for a tyrosine receptor kinase, is co-expressed with another gene after a translocation.
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