(P 263) HER2 AS A POTENTIAL NOVEL THERAPEUTIC TARGET IN SOFT TISSUE SARCOMAS

Objective: Limited options with clinical efficacy for advanced Soft Tissue Sarcoma (STS) existed and outcomes in the population with metastatic disease are generally poor. Many studies reported an over-expression of Her2 in osteosarcoma patients associated with an increased risk of tumor metastasis. No data about the role of Her2 as potential target are reported in STS. Thus, we investigated Her2 expression in different STS cell models and the potential anti-tumor effect of trastuzumab deruxtecan (T-Dx), a novel HER2/neu-targeting antibody-drug conjugate (ADC).

Methods: Her2 expression was evaluated by flow cytometry in different STS cell lines: dedifferentiated liposarcoma (SW-872), leiomyosarcoma (SK-LMS-1), gastrointestinal stromal tumor (GIST-T1), myxoid liposarcoma sensitive (402.91 WT) and resistant to trabectedin (402.91 ET) (Figure 1). As control, we used two breast cancer cell lines with high (SK-BR-3) and low Her2 expression (MCF7) (Figure 1).Tumor cell viability was analyzed after T-Dx treatment by MTT assay.

Results: Data showed that all STS cell lines were Her2 positive, but they exhibited low expression levels similar to those observed in MCF7 cells. Her2 median fluorescence intensity (MFI) is reported below: SK-BR-3 (MFI: 505261; SD 56546); MCF7 (MFI: 8735; SD 8978); SW-872 (MFI: 9621; SD 771); SK-LMS-1 (MFI: 7654; SD 245), GIST-T1 (MFI: 6238; SD 1152), 402.91 WT (MFI: 5587; SD 420), 402.91 ET (MFI: 4870; SD 831); (Figure 2). T-Dx treatment significantly affected the viability of all STS, but the rate of cell growth changed in the different cell lines (Figure 3). In particular, 402.91 WT cells were more sensitive to T-Dx treatment, while the lowest anti-tumor effect was found in GIST-T1 cells. Interestingly, a significant T-Dx cytotoxicity was observed also in trabectedin resistant cells (402.91 ET), suggesting its potential efficacy in chemo-resistant tumors (Figure 3).

Conclusion: These results showed, for the first time, an anti-tumor effect of T-Dx in STS providing the rationale for testing this novel HER2-targeting ADC in in vivo STS models.