Scientists have discovered two new genes that cause head and neck cancer patients to be resistant to chemotherapy, and that silencing either gene can make cancer cells previously unresponsive to chemotherapy subsequently respond to it.
The researchers looked through a chemical library, commonly used for drug discovery, and found two substances that could target the two genes specifically and make resistant cancer cells almost 30 times more sensitive to a common chemotherapy drug called cisplatin. They do this by reducing the levels of the two genes and could be given alongside existing chemotherapy treatment such as cisplatin. One of these substances is a fungal toxin — Sirodesmin A — and the other — Carfilzomib — comes from a bacterium. This shows that there may be existing drugs that can be repurposed to target new causes of disease, which can be cheaper than having to develop and produce new ones.
The research is the first evidence for the genes NEK2 and INHBA causing chemoresistance in head and neck squamous cell carcinoma (HNSCC) and gene silencing of either gene overturning chemoresistance to multiple drugs.
The scientists first used a method known as data mining to identify genes that may be affecting tumor responsiveness to drug therapy. They tested 28 genes on 12 strains of chemoresistant cancer cell lines, finding 4 ‘significant’ genes that were particularly responsive that they then investigated further and tested multidrug-resistance.
“Unfortunately, there are lots of people out there who do not respond to chemotherapy or radiation. But our study has shown that in head and neck cancers at least it is these two particular genes that could be behind this, which can then be targeted to fight against chemoresistance.
The two genes discovered actively ‘work’ in most human cancer types, meaning the findings could potentially extend to other cancers with elevated levels of the genes.
Neha Khera, Asvika Soodhalaagunta Rajkumar, Khlood Abdulkader M Alkurdi, Zhiao Liu, Hong Ma, Ahmad Waseem, Muy-Teck Teh. Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells. Molecular Cancer, 2023; 22 (1) DOI: 10.1186/s12943-023-01846-3
Queen Mary University of London. “New genes and natural toxins offer hope for cancer patients unresponsive to chemotherapy.” ScienceDaily. ScienceDaily, 4 September 2023. <www.sciencedaily.com/releases/2023/09/230904104625.htm>.
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