Journal Article Review Ppublish
PubMed: 39895082 DOI: 10.1093/jjco/hyaf015
Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review.
Jpn J Clin Oncol 55(4):313-326
Authors: Yuta Kubota, Masanori Kawano, Tatsuya Iwasaki, Ichiro Itonaga, Nobuhiro Kaku, Toshifumi Ozaki, Kazuhiro Tanaka
Affiliations
- Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama, Yufu City, Oita 879-5593, Japan.
- Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
- Department of Advanced Medical Sciences, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama, Yufu City, Oita 879-5593, Japan.
Abstract
In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.
MeSH
Genes, Receptor Protein-Tyrosine Kinases, Neoplasms, Sarcoma, Protein-Tyrosine Kinases, Tyrosine, Therapeutics