ArticleNPJ precision oncology2026
Clinical responses to trastuzumab deruxtecan in molecularly defined ependymoma.
Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Despite evidence that antibody drug conjugates (ADCs) are active in brain metastases, their role in primary central nervous system (CNS) tumors remains unclear. We report two adults with molecularly defined ependymoma - a MYCN-amplified spinal tumor with intracranial dissemination and a supratentorial ZFTA-RELA-fused tumor with multiple recurrences - who demonstrated radiographic response and/or durable clinical and metabolic stability with trastuzumab deruxtecan (T-DXd). HER2 expression was identified by immunohistochemistry in both tumors, consistent with prior systematic profiling of ADC targets in CNS tumors. Multiplexed imaging showed broad but heterogeneous HER2 expression across tumor states in both cases; in the MYCN-amplified tumor, this occurred alongside EGFR/MAPK-enriched proliferative niches, whereas the ZFTA-RELA tumor showed more diffuse organization without strong coupling of EGFR and proliferation. These findings provide early clinical evidence supporting HER2-directed ADCs in ependymoma and highlight the value of integrated molecular and spatial profiling in interpreting therapeutic response in rare CNS tumors.
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