How innovative gene therapy works for cancer patients resistant to chemotherapy

The battle against cancer in its different expressions is still one of the most important goals for scientists of our time. Researchers do not stop finding new mechanisms against its manifestations.

One of them reports the discovery of genes that function actively in most types of human cancer, which means that the findings could potentially be extended to others with a high presence of these genes.

Specialists at Queen Mary University of London also examined 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.

How do they work?
By lowering the levels of the two genes, the compound 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 may be cheaper than having to develop and produce new ones.

The research, led by specialists at Queen Mary and published in Molecular Cancer, is the first evidence that the NEK2 and INHBA genes cause chemoresistance in head and neck squamous cell carcinoma (HNSCC) and gene silencing of either. it overrides that opposition to multiple drugs.

Old remedies for new problems
Scientists first used a method known as data mining to identify genes that may be affecting tumor responsiveness to drug therapy. They tested 28 in 12 strains of chemoresistant cancer cell lines and found 4 significant genes that were particularly responsive. They then investigated them further and tested for multidrug resistance.

These results are a promising step for future cancer patients to receive personalized treatment based on their genes and tumor type that will give them a better survival rate and treatment outcome.

Unfortunately, there are many people who do not respond to chemotherapy or radiation. But our study has shown that, at least in head and neck cancers, it’s these two genes that could be behind it, which can then be targeted to fight chemoresistance.

Treatment that does not work is detrimental to both health systems and the patients themselves.

There can be costs associated with prolonged treatment and hospital stays, and “naturally, it is extremely difficult for people with cancer when their treatment does not have the results they expect.

90% of all head and neck cancers are caused by HNSCC, with tobacco and alcohol use being key associations.

There are 12,422 new cases of head and neck cancer each year, and the overall 5-year survival rate for patients with advanced HNSCC is less than 25%. One of the main causes of the low survival rates of HNSCC is due to treatment failure resulting from resistance to chemotherapy and/or radiation therapy.

Unlike lung and breast cancer patients, all HNSCC patients receive nearly the same treatment combinations regardless of the genetic makeup of their cancer. The specialists who were part of this research are Neha Khera, Asvika Soodhalaagunta Rajkumar, Khlood Abdulkader M Alkurdi, Zhiao Liu, Hong Ma and Ahmad Waseem.