• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.360-367
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• 2022

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor. Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion. KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.

• Journal of Chest Surgery
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• v.54 no.6
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• pp.539-542
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• 2021

Resection and reconstruction of the chest wall for the radical surgical treatment of malignant soft tissue tumors are currently considered a substantial challenge for thoracic surgeons. We present an unusual case of infantile fibrosarcoma with tropomyosin 3-neurotrophic receptor tyrosine kinase 1 fusion in a 13-year-old patient. The surgical treatment consisted of radical resection of the right posterior chest wall and reconstruction with the use of the STRATOS (Strasbourg Thoracic Osteosynthesis System) titanium rib bridge system. The patient had a favorable postoperative course and received respiratory-ventilatory rehabilitation, adjuvant therapy with chemotherapeutic agents, immunotherapy, and radiotherapy.