Novel breast cancer treatment | 研究及創新事務處

Novel breast cancer treatment: a novel small molecule that can target breast cancer stem cells and combat relapse

According to the WHO¹, breast cancer is the most prevalent cancer worldwide. There were about 2 million new cases and half a million deaths in 2020. In Hong Kong, breast cancer is the most common cancer among females². It is the third leading cause of cancer deaths among females after the lung and colon cancers². One of the biggest challenges of treating breast cancer is the presence of cancer stem cells (CSCs). CSCs are a small population of cells that are self-renewing, highly resistant to multiple cancer drugs and radiation. They are the major cause of relapse, metastasis and death. Therefore, targeting CSCs is the most effective strategy for successful eradication of cancer. However, there is no CSCs-targeting strategy available.

To address this global and local health problem, we employ our patented technology, flavonoid dimers, to target and eradicate the breast cancer stem cells (bCSCs). We discovered that two highly potent triazole-bridged flavonoid dimers were effective in reversing doxorubicin (DOX) resistance in MCF-7 CD44⁺CD24^-/lowbreast cancer stem cells (bCSCs) with an EC₅₀of 32 nM. In addition, combination of flavonoid dimers and DOX significantly inhibited the tumor growth in the MCF-7 breast cancer xenograft model compared to the DOX alone. It was found that CSCs overexpressed ROS scavenger enzyme, peroxiredoxin (PRDX1) that is associated with drug resistance and tumor progression. Flavonoid dimerswere found to inhibit the PRDX1, leading to ROS build-ups in CSCs which result in the reversal of drug resistance. This work provided a new insight into the drug resistance mechanism of CSCs and provided a novel combination chemotherapy to treat breast cancers by eradicating the CSCs.

Our combination treatment targets both regular cancer cells and cancer stem cells. It could be an effective chemotherapy that can shrink tumor, prevent relapse/metastasis, prolong the disease-free survival time of cancer patients and reduce the cancer-related death.

¹WHO 2020 ² Department of Health, HKSAR

Novel breast cancer treatment a novel small molecule

Principal Investigator

Prof. Larry M. C. Chow

Head and Professor, Department of Applied Biology and Chemical Technology

Technology Features:

Novel combination chemotherapy for breast cancer treatment: flavonoid dimer + conventional chemo drugs

High potency: nanomolar (nM) range of EC₅₀ at cellular level and 90% reduction of tumor volume in animals.

Safety: there was no death and significant body weight loss in animals. No drug-drug interaction was observed.
Low production cost: flavonoid dimers are small molecules with simple synthesis route.
Versality: it can treat all subtypes of breast cancer, “One-size-fits-all” cancer treatment. Bigger market size and more profits compared to conventional hormonal therapy that only targets the ER positive subtype.