Personalized pharmacokinetic-pharmacodynamic guided therapy via an induced pluripotent stem cell-derived multi-organoid platform in NF1-mutant breast cancer - PubMed
12 hours ago
- #personalized therapy
- #organoid platform
- #NF1-mutant breast cancer
- Personalized treatment model using a patient-derived Networking Organoid Culture System (NOCS) composed of intestinal, liver, and kidney organoids differentiated from induced pluripotent stem cells (iPSCs).
- Multi-organoid system enabled individualized assessment of drug absorption, distribution, metabolism, and excretion.
- Integrative genomic and pathway analyses uncovered therapeutic vulnerabilities, including responsiveness to a novel exon skipping therapy targeting NF1.
- PK/PD-guided screening on the NOCS prioritized Paxalisib, which, when combined with the exon skipping approach, demonstrated synergistic anticancer efficacy.
- Established a clinically relevant framework integrating multi-organ PK/PD modeling with genotype-driven therapeutic strategies.
- Potential of combining targeted gene correction with small-molecule therapy for personalized treatment.