non-small cell lung cancer (NSCLC)immunohistochemistry (IHC)incidencefluorescence in situ hybridization (FISH)Background: We performed a retrospective analysis to determine the incidence of neurotrophic tropomyosin-receptor kinase (NTRK) fusion in non-small cell lung cancer (NSCLC). Methods: Archival ...
These mutations commonly reside in the catalytic region of the kinase domain, and include residues in the solvent front of the ATP-binding pocket (solvent-front mutations), the gatekeeper residue that is a conserved hydrophobic amino acid in the active site (gatekeeper mutation), or the amino ...
(refractory). Regorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps to slow or stop the spread of cancer cells. Venetoclax is in a class of medications called B-cell lymphoma...
One significant mutation driving oncogenesis in various cancers, including NSCLC, is the neurotrophic tyrosine receptor kinase (NTRK) fusion. Presently, larotrectinib and entrectinib are the only FDA-approved therapies for NTRK-mutated cancers. Despite the efficacy and tolerability exhibited by ...
Oncogenic NTRK activation can result from mutation, CNVs, overexpression, and translocations [10]. NTRK fusion proteins are typically created by chromosomal rearrangements forming hybrid genes in which the 5’ end of the partner gene is joined to the 3’ portion of NTRK1, NTRK2, or NTRK3,...
Repotrectinib has also shown significant efficacy in ROS1 fusion-positive non¬–small cell lung cancer (NSCLC), which was also studied in the TRIDENT-1 trial. The FDA has approved repotrectinib (Augtyro; Bristol Myers Squibb), a next-generation tyrosine kinase inhibitor (...
Selitrectinib is a pan-Trk inhibitor with minimal activity against other kinases. It is effective in the treatment of tumours withNTRKfusions that have developed resistance to first-generation Trk inhibitors in the form of a secondary point mutation in the kinase domain [53]. Two ongoing phase...
The FDA granted accelerated approval to entrectinib (Rozlytrek) for the treatment of pediatric patients 1 month and older with solid tumors that have anNTRKgene fusion without an acquired resistance mutation, are metastatic, are not favorable candidates for surgical resection, and have disease...
rare (P < 0.001) andNTRKfusion-positive tumors often had a lower tumor mutation burden (TMB) (P < 0.001)17. A similar study of 87 patients withNTRK1–3fusions also showed that these alterations were mutually exclusive with strong MAPK driver mutations inKRAS, BRAF,NRAS, andEGFR...
3One complete response was observed in a patient with CNS tumors and anETV6-NTRK3gene fusion, a second was observed in a patient with no CNS tumors and aDCTN1-ALKgene fusion, and a third in a patient with neuroblastoma harboring anALKF1174L mutation. “Today’s approval ...