Published on Tue Aug 10 2021

Patient-derived triple negative breast cancer organoids provide robust model systems that recapitulate tumor intrinsic characteristics

Bhatia, S., Kramer, M., Russo, S., Naik, P., Arun, G., Brophy, K., Andrews, P. A., Fan, C., Perou, C. M., Preall, J., Ha, T., Rishi, A., Wilkinson, J. E., McCombie, W. R., Kostroff, K., Spector, D. L.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes. There is an unmet clinical need for targeted therapies and better model systems.

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Abstract

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, and an unmet clinical need for targeted therapies and better model systems. Here, we developed and comprehensively characterized a diverse biobank of normal and breast cancer patient-derived organoids (PDOs) with a focus on TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBCs). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibit signatures of aggressive MYC-driven basal-like breast cancers and are largely comprised of luminal progenitor (LP)-like cells. The TNBC LP-like cells are distinct from normal LPs and exhibit hyperactivation of NOTCH and MYC signaling. Overall, our study validates TNBC PDOs as robust models for understanding breast cancer biology and progression, paving the way for personalized medicine and better treatment options.