Researchers from Queen Mary University of London have identified two new genes that make patients with head and neck cancer resistant to chemotherapy. By suppressing one of these genes, cancer cells that were previously resistant to chemotherapy can now respond to it.
The two genes were shown to actively "work" in the majority of human cancer types, suggesting that the discoveries might apply to additional malignancies with high quantities of the genes.
The researchers also 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, led by Queen Mary and published in Molecular Cancer, 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 tumour 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.
Dr Muy-Teck Teh, senior author of the study from Queen Mary University of London, said: “These results are a promising step towards cancer patients in the future receiving personalised treatment based on their genes and tumour type that give them a better survival rate and treatment outcome.
“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.
“Treatment that doesn’t work is damaging both for the NHS and patients themselves. There can be costs associated with prolonged treatment and hospital stays, and it’s naturally extremely difficult for people with cancer when their treatment doesn’t have the results they are hoping for.”
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