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Tenosynovial giant cell tumors (TGCT): molecular biology, drug targets and non-surgical pharmacological approaches. | LitMetric

AI Article Synopsis

  • * The CSF1-CSF1R pathway is the main focus for treatment, with Pexidartinib being the only FDA-approved drug, though its use is questioned due to side effects and lack of European approval.
  • * There is a need for safer and more effective therapies, particularly for patients with diffuse-type TGCT who may not benefit from surgery; future research should focus on targeting the tumor cells directly.

Article Abstract

Introduction: Tenosynovial giant cell tumor (TGCT) is a mono-articular, benign or locally aggressive and often debilitating neoplasm. Systemic therapies are becoming part of the multimodal armamentarium when surgery alone will not confer improvements. Since TGCT is characterized by colony-stimulating factor-1 () rearrangements, the most studied molecular pathway is the CSF1 and CSF1 receptor (CSF1R) axis. Inhibiting CSF1-CSF1R interaction often yields considerable radiological and clinical responses; however, adverse events may cause treatment discontinuation because of an unfavorable risk-benefit ratio in benign disease. Only Pexidartinib is approved by the US FDA; however, the European Medicines Agency has not approved it due to a uncertain risk-benefit ratio. Thus, there is a need for safer and effective therapies.

Areas Covered: Light is shed on disease mechanisms and potential drug targets. The safety and efficacy of different systemic therapies are evaluated.

Expert Opinion: The CSF1-CSF1R axis is the principal drug target; however, the effect of CSF1R inhibition on angiogenesis and the role of macrophages, which are essential in the postoperative course, needs further elucidation. Systemic therapies have a promising role in treating mainly diffuse-type, TGCT patients who are not expected to clinically improve from surgery. Future drug development should focus on targeting neoplastic TGCT cells.

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Source
http://dx.doi.org/10.1080/14728222.2022.2067040DOI Listing

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