Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways

Chenyu Zhou; Murni Nazira Sarian; Xiaohui Tong; Rongchun Han; Theebaa Anasamy; Hamizah Shahirah Hamezah

doi:10.1016/j.jpha.2025.101538

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Chenyu Zhou, Murni Nazira Sarian, Xiaohui Tong, Rongchun Han, Theebaa Anasamy, Hamizah Shahirah Hamezah. Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101538

Citation:

Chenyu Zhou, Murni Nazira Sarian, Xiaohui Tong, Rongchun Han, Theebaa Anasamy, Hamizah Shahirah Hamezah. Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101538

Citation:

Chenyu Zhou, Murni Nazira Sarian, Xiaohui Tong, Rongchun Han, Theebaa Anasamy, Hamizah Shahirah Hamezah. Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101538

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Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways

doi: 10.1016/j.jpha.2025.101538

a. Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia;
b. School of Life Sciences, Anhui University of Chinese Medicine, Hefei 230012, China;
c. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
d. Faculty of Medicine, Manipal University College Malaysia (MUCM), Jalan Padang Jambu, Bukit Baru, 75150 Melaka, Malaysia

Funds:

This work was supported by Universiti Kebangsaan Malaysia under Dana Impak Perdana 2.0 Research Grant to HSH (Grant No.: DIP-2024-021). The Manipal University CollegeMalaysia under MUCM-MRB Joint Seed Grant to TA (Grant No.: MUCM-MRB/002/2024) also supported this work. Fig. 1, Fig. 2, Fig. 3, Fig. 4 and the graphical abstract were created by using BioRender.com (https://www.biorender.com) under a publication license.

Received Date: Jun. 16, 2025
Accepted Date: Dec. 22, 2025
Rev Recd Date: Dec. 18, 2025
Available Online: Jan. 10, 2026

Abstract

Abstract

Halogenated anthraquinone derivatives have good potential in addressing the major clinical challenges associated with anthracyclines for breast cancer, including high toxicity, low selectivity, and drug resistance issues. By analyzing the structure-activity relationships of these compounds, the review highlights how specific structural modifications may enhance therapeutic efficacy. A comprehensive overview is also provided to categorize breast cancer progression across stages 0 to IV, along with therapeutic approaches for each of the three basic molecular subtypes, with placing particular focus on triple-negative breast cancer. This review details how anthraquinone derivatives modulate the vascular endothelial growth factor (VEGF)-related signaling pathways and regulate the expression of key proteins and chemokines, thereby inhibiting endothelial cell function during tumor angiogenesis, suppressing cancer cell migration and immune evasion in breast cancer. Studies on halogenated anthraquinone derivatives in anticancer applications between 2013 and 2025 are summarized, and the cutting-edge therapeutic strategies that have contributed to the development of anthraquinone derivatives are highlighted. The high approval rate of halogen-containing drugs released by the U.S. Food and Drug Administration in 2024, alongside their promising therapeutic efficacy in oncology, has once again drawn the attention of researchers. Overall, the contributions of halogen substitution to molecular stability, target specificity, and resistance to metabolic degradation highlight the significant potential of halogenated anthraquinone derivatives in the development of novel therapeutics for breast cancer.
- Breast cancer,
- Anti-angiogenesis,
- VEGF pathway,
- Structure-activity relationships,
- Halogenated anthraquinones

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References(146)

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