# An integrated study combining network toxicology machine learning and molecular simulation reveals the molecular mechanisms of permanent hair dyes in breast cancer

## TL;DR

This study combines machine learning and molecular simulations to uncover how permanent hair dye ingredients may contribute to breast cancer development.

## Contribution

The study introduces an integrated approach using network toxicology and machine learning to identify key molecular targets linking hair dyes to breast cancer.

## Key findings

- Eight key targets (e.g., HSP90AA1, CDK1) were identified as regulators of breast cancer progression linked to hair dye ingredients.
- Disperse Yellow 3 showed the strongest binding affinity to key targets, indicating a strong association with breast cancer risk.
- Machine learning confirmed the prognostic importance of SRC, HSP90AB1, HSP90AA1, and CDK1 in breast cancer.

## Abstract

Permanent hair dyes have been linked to an increased risk of breast cancer (BC), though the underlying mechanisms remain unclear. To address this knowledge gap, our investigation employed an integrated approach combining network toxicology, molecular docking, molecular dynamics simulations, and machine learning to decipher the molecular mechanisms by which permanent hair dyes might promote BC pathogenesis. Five permanent hair dye ingredients classified by IARC as carcinogenic were included in this study: p-phenylenediamine, resorcinol, pyridine, Disperse Yellow 3, and HC Blue No. 2. These chemicals can regulate BC progression through various signaling pathways, with key core targets identified as HSP90AA1, HSP90AB1, ESR1, CDK1, STAT3, MAPK8, HDAC1, and SRC. A machine learning model comprising 128 algorithms confirmed that these eight targets possess strong prognostic predictive capabilities for BC. Subsequent SHAP analysis revealed SRC, HSP90AB1, HSP90AA1 and CDK1 as the key contributors to prognostic prediction, with each being highly expressed in BC and linked to poor clinical prognosis. Notably, among all chemicals screened, Disperse Yellow 3 exhibited the strongest binding affinity to these four key targets, demonstrating the strongest association with BC risk.

The online version contains supplementary material available at 10.1007/s12672-026-04585-1.