Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor...

Area of Science:

• Oncology
• Cell Biology
• Genomics

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited treatment options.
• There is a critical need for advanced model systems that accurately recapitulate TNBC heterogeneity and biology for research and therapeutic development.

Purpose of the Study:

• To develop and characterize a biobank of patient-derived organoids (PDOs) from normal and triple-negative breast cancer (TNBC) samples.
• To investigate the cellular composition, intrinsic properties, and long-term culture potential of TNBC PDOs.
• To identify key cellular and molecular drivers of TNBC progression using single-cell profiling.

Main Methods:

• Creation and comprehensive characterization of a diverse biobank of patient-derived organoids (PDOs).
• Long-term propagation of a subset of TNBC PDOs (LT-TNBC).
• Single-cell profiling (e.g., single-cell RNA sequencing) to analyze cell types and gene expression patterns.

Main Results:

• TNBC PDOs successfully recapitulated the intrinsic properties of patient tumors.
• A subset of TNBC PDOs were established for long-term culture (LT-TNBC).
• Single-cell analysis revealed distinct cell populations within TNBC PDOs, identifying candidates associated with cancer progression, including hyperactivated NOTCH and MYC signaling in luminal progenitor-like cells.

Conclusions:

• TNBC PDOs serve as robust and valuable preclinical models for studying breast cancer biology and progression.
• These models offer a platform for understanding TNBC heterogeneity and identifying therapeutic targets.
• The findings support the advancement of personalized medicine strategies for TNBC patients.