Foretinib Overcomes Entrectinib Resistance Associated with the NTRK1 G667C Mutation in NTRK1 Fusion-Positive Tumor Cells in a Brain Metastasis Model

• Published in: Clinical cancer research Vol. 24; no. 10; pp. 2357 - 2369
• Main Authors: Nishiyama, Akihiro, Yamada, Tadaaki, Kita, Kenji, Wang, Rong, Arai, Sachiko, Fukuda, Koji, Tanimoto, Azusa, Takeuchi, Shinji, Tange, Shoichiro, Tajima, Atsushi, Furuya, Noritaka, Kinoshita, Takayoshi, Yano, Seiji
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.05.2018
• Subjects: Amino Acid Substitution; Anilides - chemistry; Anilides - pharmacology; Animal models; Animals; Benzamides - chemistry; Benzamides - pharmacology; Brain; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain tumors; Cancer; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Central nervous system; Clinical trials; Colon; Colon cancer; Colorectal cancer; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm - drug effects; Enzyme inhibitors; Experimental design; Gene fusion; Gene rearrangement; Heterografts; Humans; Indazoles - chemistry; Indazoles - pharmacology; Liver; Medical research; Metastases; Metastasis; Mice; Mimicry; Models, Molecular; Mutation; NTRK1 gene; Oncogene Proteins, Fusion - genetics; Organs; Patients; Phosphorylation; Proteins; Quinolines - chemistry; Quinolines - pharmacology; Receptor, trkA - chemistry; Receptor, trkA - genetics; Structure-Activity Relationship; Tropomyosin; Tumor cells; Tumors; Tyrosine; Viability

Rearrangement of the neurotrophic tropomyosin receptor kinase 1 ( ) gene, which encodes tyrosine receptor kinase A (TRK-A), occurs in various cancers, including colon cancer. Although entrectinib is effective in the treatment of central nervous system (CNS) metastases that express fusion proteins, a...