Two Genes Behind Chemoresistance in Head and Neck Cancer

Researchers at Queen Mary University of London have identified a pair of novel genes responsible for rendering head and neck cancer patients resistant to chemotherapy. Moreover, they have determined that suppressing either of these genes can render cancer cells, which were previously unreactive to chemotherapy, susceptible to treatment. These two genes are actively involved in the majority of human cancer types, implying that these discoveries might have implications for other cancers exhibiting elevated levels of these genes.

The researchers also sifted through a chemical library commonly used for drug discovery and found two substances that could target these genes specifically, making resistant cancer cells nearly 30 times more sensitive to a common chemotherapy drug known as cisplatin. These substances achieve this by reducing the levels of the two genes and could be administered alongside existing chemotherapy treatments, such as cisplatin.

One of these substances is a fungal toxin called Sirodesmin A, while the other, Carfilzomib, is derived from a bacterium. This highlights the potential of repurposing existing drugs to target new causes of disease, which can be a cost-effective alternative to developing and producing entirely new medications.

This research, led by Queen Mary and published in Molecular Cancer, provides the first evidence that the genes NEK2 and INHBA cause chemoresistance in head and neck squamous cell carcinoma (HNSCC), and silencing either gene can reverse chemoresistance to multiple drugs.

Data Mining: A Methodology to Identify the Chemoresistant Genes

To identify genes that may influence tumor responsiveness to drug therapy, the scientists initially employed a method known as data mining. They subsequently tested 28 genes on 12 strains of chemoresistant cancer cell lines, identifying four "significant" genes that showed particular responsiveness and further investigated their role in multidrug resistance.

Dr. Muy-Teck Teh, the senior author of the study from Queen Mary University of London, commented, "These results are a promising step towards cancer patients in the future receiving personalized treatment based on their genes and tumor type, which could improve their survival rates and treatment outcomes. Unfortunately, there are many individuals who do not respond to chemotherapy or radiation.

However, our study suggests that in head and neck cancers, these two specific genes could be the culprits, and targeting them could combat chemoresistance. Ineffective treatments are detrimental both to the NHS and patients themselves. Prolonged treatment and hospital stays can result in additional costs, and it is naturally disheartening for cancer patients when their treatment fails to yield the desired results."

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Approximately 90% of all head and neck cancers are caused by HNSCCs, with tobacco and alcohol use being significant risk factors. Each year, there are 12,422 new cases of head and neck cancer, and the overall 5-year survival rate for patients with advanced HNSCC is less than 25%. A major contributor to these poor survival rates in HNSCC is treatment failure stemming from resistance to chemotherapy and/or radiotherapy (1^✔ ✔Trusted Source
Head and neck cancers statistics

Go to source).

Unlike lung and breast cancer patients, who often receive tailored treatments based on the genetic makeup of their cancer, all HNSCC patients currently undergo almost identical combinations of treatment.

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Reference:

1. Head and neck cancers statistics - (https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/head-and-neck-cancers)

Source-Eurekalert