For the first time, researchers have pinpointed two genes – NEK2 and INHBA – that are resistant to chemotherapy for head and neck cancers, and found that by silencing them, treatment can be far more effective.
The genes, which contribute to chemo resistance in head and neck squamous cell carcinoma (HNSCC), can potentially be quietened down to allow existing therapies to do their job.
“Unfortunately, there are lots of people out there who do not respond to chemotherapy or radiation,” said senior author Teh Muy-Teck, from Queen Mary University of London. “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.”
Around 90% of head and neck cancers are caused by HNSCCs, and the survival rate of patients with advanced HNSCC is less than 25%, largely due to it being resistant to treatment, including radiotherapy and chemotherapy. There are, to date, no targeted treatments that take genetic makeup into account.
The researchers tested 28 genes on 12 strains of chemoresistant cancer cell lines, landing on four that required further investigation. They also looked through a ‘chemical library,’ used for developing new therapeutics, and found that the NEK2 and INHBA genes could be suppressed using fungal toxin Sirodesmin A and Carfilzomib, which is sourced from bacteria.
In two of those four genes, NEK2 and INHBA, the researchers were able to use Sirodesmin A and Carfilzomib to make HNSCC cancer cells nearly 30 times more vulnerable when treated with the common chemotherapy drug cisplatin.
And with Sirodesmin A and Carfilzomib already used in therapeutics, the researchers are hopeful that they can be ‘repurposed’ and adapted to complement treatment in order to suppress NEK2 and INHBA and offer more effective chemotherapy outcomes.
“These results are a promising step towards cancer patients in the future receiving personalized treatment based on their genes and tumor type that give them a better survival rate and treatment outcome,” said Muy-Teck.
The study was published in the journal Molecular Cancer.
Source: Queen Mary University of London
