A research team led by Henry Kwok Hang Fai, associate professor in the Faculty of Health Sciences (FHS) of the University of Macau (UM), has made significant progress in a novel application strategy for the anti-cancer drug Homoharringtonine (HHT). The study has clarified the mechanisms underlying HHT activity against bladder cancer growth and shows the enormous potential of HHT as an anti-cancer agent, which could be applied as a combination treatment strategy for bladder cancer. The research results have been published in the internationally renowned journal Pharmacological Research.
Bladder cancer is among the top ten cancers worldwide. 25 per cent of patients were diagnosed with invasive bladder cancer or metastasis disease for the first time, and the five-year survival rate was only 5 per cent. Once the patients are diagnosed with bladder cancer, they will face limited treatment options and a complex, long-term care pathway. Furthermore, bladder cancer has the highest recurrence rate amount all cancer types. For this reason, patients of this cancer have low quality of life and the therapy is usually more complicated than that for other cancer patients.
Applying immune checkpoint inhibitors and FGFR protein tyrosine kinase inhibitors in bladder cancer therapy provides an opportunity to improve outcomes for patients with high-grade metastatic cancer. However, most bladder cancer patients in all stages do not respond to immunotherapy, and drug-resistant problems occur often in patients with recurrence. There is an urgent need for renewal agents or treatments as new options for patients with bladder cancer. For a new drug to enter the market, there is a long development cycle with high costs and low success rates.
HHT has been used for hematologic malignancies for over 40 years in China and was approved by the United States Food and Drug Administration (FDA) in 2012 as an anti-leukemia drug. Many studies have demonstrated that HHT effectively inhibits the development of several types of solid tumours, although the underlying mechanisms of action are unclear. In this study, Prof Kwok’s research team investigated the mechanisms underlying HHT activity against bladder cancer growth. The research team compared HTT with the drugs currently used clinically for bladder cancer treatment. HHT showed more potent inhibitory activity than cisplatin, carboplatin, and doxorubicin. The in vitro and in vivo data demonstrated that HHT inhibited proliferation, colony formation, migration, and cell adhesion of bladder cancer cells and induced apoptosis and cell cycle arrest in the nanomolar concentration range. Furthermore, the research team revealed that HHT treatment could downregulate the MAPK/Erk and PI3k/Akt signaling pathways by inactivating the integrin α5/β1-FAK/Src axis. In addition, HHT-induced activity reduced cell-extracellular matrix (ECM) interactions and cell migration, thus suppressing tumour metastasis progression.
Prof Kwok is the corresponding author of this study and his PhD student Wu Qiushuang is the first author. In addition, Zhang Qingwen, associate professor in UM’s Institute of Chinese Medical Sciences, also made important contributions to this study. The study was supported by the Science and Technology Development Fund, Macao SAR (File no: 0010/2021/AFJ, 0027/2022/A1), the Guangzhou Science and Technology Innovation Funding (File no: 201807010096) and UM (File no: MYRG2019-00150-ICMS). The full version of the research study can be viewed at https://doi.org/10.1016/j.phrs.2023.106654.
| Source: Faculty of Health Sciences | |
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