Performance comparison across models.

Anticancer peptides (ACPs) are short bioactive sequences that selectively target tumor cells with minimal toxicity, positioning them as promising candidates for next-generation cancer therapies. However, existing computational models face limitations in sequence representation and class imbalance. To address these challenges, we propose UACD-ACPs, a unified fusion-driven framework that integrates a diffusion-inspired noise-conditioned classifier for ACP prediction and a diffusion-based peptide generation module with cancer-type-aware organization for targeted downstream screening. The classification module integrates ProtBERT-based semantic embeddings with physicochemical descriptors via the Multiscale Embedding Compression Strategy (MECS) and a diffusion-inspired noise-conditioned encoder, substantially enhancing predictive robustness and accuracy, particularly under challenging imbalanced multi-class settings. In the generative pipeline, we introduce a denoising diffusion-based generative framework augmented by two novel fusion modules: the Bitemporal Fusion Module (BFM) and the Temporal Feature Attention Module (TFAM). These modules perform multi-scale temporal and semantic fusion to promote the generation of structurally coherent and functionally relevant peptide candidates. Experimental results demonstrate that UACD-ACPs outperforms state-of-the-art methods in terms of accuracy, F1-score, and AUC-ROC. The generated peptides exhibit favorable physicochemical properties, diverse secondary structures, and strong structural stability, as validated by molecular dynamics simulations and membrane-binding analyses. Overall, this study highlights the potential of fusion-driven diffusion-based frameworks for alleviating class imbalance and data heterogeneity in anticancer peptide modeling, paving the way for scalable and biologically grounded ACP discovery.