2022
DOI: 10.1158/0008-5472.can-21-2807
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Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor Intrinsic Characteristics

Abstract: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, highlighting the 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 (PDO) with a focus on TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBC). Single cell profiling of PDOs identified cell… Show more

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Cited by 41 publications
(33 citation statements)
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“…Kim et al 109 explored the pathway activity, microenvironment and clinical relevance of TNBC in their own biobank, and systematically proposed a predictive model and prognostic markers. Another tumor organoid biobank of TNBC provided comprehensive genome, transcriptome, and cellular characterization 110 . TNBC organoids lost the characteristics of normal breast PDO and were mostly rich in luminal progenitor cells.…”
Section: Overview Of Pdto Biobanksmentioning
confidence: 99%
“…Kim et al 109 explored the pathway activity, microenvironment and clinical relevance of TNBC in their own biobank, and systematically proposed a predictive model and prognostic markers. Another tumor organoid biobank of TNBC provided comprehensive genome, transcriptome, and cellular characterization 110 . TNBC organoids lost the characteristics of normal breast PDO and were mostly rich in luminal progenitor cells.…”
Section: Overview Of Pdto Biobanksmentioning
confidence: 99%
“…After organoid coculture with pre-activated autologous CD8+ T cells, MAL2 depletion was found to enhance CD8+ T cell cytotoxicity [ 26 ]. Furthermore, Bhatia et al, developed long-term TNBC patient-derived organoids that imitated the extensively studied and evidently proven features of this aggressive MYC-driven, basal-like breast cancer and were largely comprised of luminal progenitor-like cells exhibiting hyperactivation of NOTCH and MYC signaling [ 27 ], while Chew et al, described low or undetectable Fibroblast Growth Factor Receptor 4 (FGFR4) immunohistochemical staining in TNBC patient-derived organoids [ 28 ]. Altogether, the study of TNBC patient-derived organoids may pave the way for novel and reliable discoveries in the field of TNBC pathogenesis that other in vitro or even in vivo culture models do not allow.…”
Section: The Role Of Patient-derived Organoids In the Understanding O...mentioning
confidence: 99%
“…Furthermore, approximately 5–10% of the most aggressive form of breast cancer, triple negative breast cancer (TNBC), is associated with NRR or PEST domain mutations in NOTCH1 and NOTCH2 [ 37 , 38 ], but TNBC is also associated with elevated expression of JAGGED1, NOTCH1, NOTCH3 or NOTCH4, which in turn is associated with poor clinical prognosis [ 39 , 40 , 41 , 42 ]; for review see [ 43 ]. TNBC patient-derived organoids show hyperactivated Notch signaling in comparison to control organoids [ 44 ]. In other forms of breast cancer, such as estrogen receptor (ER)- or HER2-positive breast cancer, Notch signaling may initially be lower, but increases in response to endocrine therapies aiming at reducing ER activity or to therapy using HER2-blocking antibodies (trastuzumab) [ 45 , 46 , 47 , 48 , 49 , 50 ]; for review see [ 51 ].…”
Section: Dysregulated Notch Signaling In Cancermentioning
confidence: 99%