CSF1R overexpression

In conclusion, our findings indicate that overexpression of Csf1r leads to the generation of osteosarcoma tumors with reduced immune presence. This is significant because previous studies have shown that reduced immune presence in osteosarcoma and other sarcoma types is associated with poor patient outcomes. By therapeutically increasing CSF1 levels within tumors, we may promote the proliferation and differentiation of immune cells, potentially improving patient outcomes.

In Asian patients with symptomatic TGCT not amenable to improvement with surgery, pexidartinib demonstrated clinical benefit in tumor response and improvement in joint function. The overall safety profile of pexidartinib was comparable with previous data. Hepatotoxicity was manageable with frequent liver test monitoring and dose modifications as defined in the protocol, and no new safety signals were observed in this Asian population.

With the extension of treatment duration, there is an observed augmentation in the number of pts experiencing sustained tumor shrinkage and favorable safety of Pimicotinib with no apparent hepatotoxicity. Current data confers durable therapeutic benefits in TGCT pts, suggesting that prolonged exposure may represent an optimal treatment approach. In addition, a separate cohort with prior anti-CSF-1/CSF-1R therapies is underway to assess the safety and antitumor activity.

Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.