Abstract 286: Patient derived explant culture (PDEC) as a model for treatment resistant ERα positive breast cancers

Abstract

Abstract Breast cancer is the most frequent cancer and leading causes of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα+) phenotype that is initially responsive to antihormonal therapies, but often drug resistance emerges. Three-dimensional ex vivo cultures from patient-derived tumor tissue offer new opportunities for drug development and personalized treatment of cancer. However, one of the main challenges in establishing a tumor type faithful ex vivo tissue culture system is in optimization of biochemical and physical microenvironment to preserve desired phenotypic features. The ERα+ phenotype is not stable in cultured cells for reasons not fully understood. Together with Helsinki University Hospital we examined 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. In our current study we have utilized the PDEC model to identify novel biomarkers that could predict the emergence of tamoxifen resistance in primary breast tumors. Citation Format: Pauliina Munne, Iiris Räty, Aino Peura, Linda Patrikainen, Denis Belitskin, Juha Klefstrom. Patient derived explant culture (PDEC) as a model for treatment resistant ERα positive breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 286.