(P 61) HER2 TARGETING IN CHORDOMA: PRECLINICAL INSIGHTS ON TRASTUZUMAB DERUXTECAN

Objective: Chordomas are rare malignant tumors with limited therapeutic options, particularly in advanced disease. Although HER2 (human epidermal growth factor receptor 2) is a well-established target in several cancers, its expression and potential role in chordoma remain unexplored. Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, has demonstrated efficacy across HER2-expressing tumors. In this study, we aim to investigate HER2 expression in chordoma and evaluate the therapeutic potential of trastuzumab deruxtecan in relevant cell models.

Methods: HER2 expression was analyzed by flow cytometry in three chordoma cell lines: CH-22, U-CH17 and U-CH14. The HER2-amplified breast cancer cell line SK-BR-3 was used as a positive control. T-DXd cytotoxicity was assessed by measuring cell viability via flow cytometry.

Results: Flow cytometry analysis revealed that all three chordoma cell lines were HER2-positive. Median fluorescence intensity (MFI) values were as follows: SK-BR-3 (MFI: 505261; SD: 56,546), CH-22 (MFI: 2379; SD: 327), U-CH17 (MFI: 1791; SD: 371), and U-CH14 (MFI: 1607; SD: 259). Treatment with trastuzumab deruxtecan (T-DXd) was performed on CH-22 and U-CH17 cells and significantly reduced cell viability in both lines. However, sensitivity to T-DXd varied, with CH-22 cells exhibiting greater susceptibility (IC₅₀: 7.2 µg/mL) compared to U-CH17 cells (IC₅₀: 55.3 µg/mL).

Conclusion: Chordoma cell lines exhibit measurable HER2 expression and treatment with trastuzumab deruxtecan significantly reduced cell viability, particularly in CH-22 cells. These findings suggest HER2 as a promising therapeutic target in chordoma and support further investigation of HER2-directed therapies in preclinical and clinical studies.