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   Multi-omics and histological assessment to identify patient-derived xenograft models of invasive lobular carcinoma    

Invasive lobular carcinoma (ILC), the second most common subtype of breast cancer, is underrepresented in research due to the scarcity of relevant preclinical models. Characterized by loss of E-cadherin (CDH1), ILC exhibits distinct biological behavior compared to invasive ductal carcinoma (NST), yet most available PDX models derive from the latter. A lack of ILC-specific models has limited the development of targeted therapies.

In collaboration with the University of Pittsburgh, Champions Oncology leveraged the Lumin® platform to perform multi-omics and pathology-based characterization of breast cancer PDX models to identify and validate ILC-specific models.

• By integrating genomic (WES, RNA-seq) and clinical data from 128 breast cancer models, researchers identified 7 putative ILC models based on CDH1 mutations, low E-cadherin expression, and histopathological reclassification.

• Molecular analysis revealed enrichment of luminal PAM50 subtypes and recurrent alterations in genes such as PIK3CA, FOXA1, PTEN, and CDH1 in ILC models—offering insight into subtype-specific oncogenic pathways.

• Pathological validation, including immunohistochemistry for E-cadherin, p120, ER, PR, and HER2, confirmed the ILC phenotype in selected models, establishing a robust framework for future ILC research and preclinical drug testing.