Speaker
Description
Intratumoral heterogeneity in breast cancer is a major challenge for prognosis and treatment, yet the dynamical mechanisms underlying subtype transitions remain poorly understood. Using a gene regulatory network model calibrated with experimental data, we show that stochastic variability in NF-κB can induce irreversible switching from HER2+ to TNBC states, providing a dynamical mechanism for intratumoral heterogeneity \cite{Lopes2025}. The model reproduces HER2+ and TNBC as distinct stable states within a common regulatory framework, consistent with in vitro expression patterns and further supported by patient-derived bulk and single-cell data. Because these transitions occur asynchronously across cells, the model predicts the coexistence of HER2+ and TNBC subtypes within the same tumor, linking molecular stochasticity to tissue-level heterogeneity. These results provide a mechanistic framework for understanding how subtype heterogeneity may emerge during tumor progression and may help inform strategies for classification and therapeutic intervention.
Bibliography
@article{Lopes2025,
author = {Lopes, F. and Pires, B. R. B. and Lima, A. A. B.},
title = {NF-kappaB epigenetic attractor landscape drives breast cancer heterogeneity},
journal = {npj Systems Biology and Applications},
year = {2025},
volume = {11},
pages = {135},
doi = {10.1038/s41540-025-00611-0}
}
