Study gives more insight into head, neck cancer patients resistance to chemotherapy

Washington: Two new genes have been discovered by Queen Mary University of London researchers that render people with head and neck cancer resistant to chemotherapy. Cancer cells that were previously resistant to chemotherapy can now respond to it by silencing one of these genes.

The two genes were demonstrated to actively "work" in the majority of known kinds of human cancer, indicating that the discovery may also be applicable to other cancers with high gene expression levels.

Additionally, the researchers searched through a chemical library, a tool frequently used in drug discovery, and discovered two compounds that may specifically target the two genes and render cancer cells resistant to the chemotherapy medication cisplatin approximately 30 times more susceptible to it.

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."