| _version_ | 1867020348293120000 |
|---|---|
| author | Abigail G Parrish Frank Szulzewsky |
| author_facet | Abigail G Parrish Frank Szulzewsky Abigail G Parrish Frank Szulzewsky |
| collection | Wiley Open Access |
| contents | TRKing down drug resistance in NTRK fusion‐positive cancers† Abigail G Parrish Frank Szulzewsky The Journal of Pathology AbstractIn a recent issue of The Journal of Pathology, Chen and colleagues established novel patient‐derived ex vivo models of NTRK fusion‐positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine kinase inhibitors. Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents. © 2024 The Pathological Society of Great Britain and Ireland. 10.1002/path.6341 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/path.6341 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6341 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | TRKing down drug resistance in NTRK fusion‐positive cancers† Abigail G Parrish Frank Szulzewsky The Journal of Pathology TRKing down drug resistance in NTRK fusion‐positive cancers† Abigail G Parrish Frank Szulzewsky The Journal of Pathology AbstractIn a recent issue of The Journal of Pathology, Chen and colleagues established novel patient‐derived ex vivo models of NTRK fusion‐positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine kinase inhibitors. Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents. © 2024 The Pathological Society of Great Britain and Ireland. 10.1002/path.6341 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | TRKing down drug resistance in NTRK fusion‐positive cancers† |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6341 |