New method may help more patients with head, neck cancers

Not all cancers are the same, even when they originate from the same site. This is why some patients respond strongly to some treatments, while others do not.

For example, a trial conducted in Singapore found that only 3 per cent to 5 per cent of patients with head and neck cancers responded very well to a drug developed for lung cancer.

Now, a seven-member team from the National Cancer Centre Singapore (NCCS) may have found a way to help more patients with head and neck cancers respond better to treatment by introducing a specific protein into their bloodstream.

This has proven to be a resounding success in laboratory experiments and in mice, with the tumours shrinking to the point of non-existence.

The next step is to take it from bench to bedside with clinical trials in patients, to find the best dosage and assess how well it works.

If the treatment works as expected, it has the potential to treat other cancers, too.

Head and neck cancers – which occur in areas between the nose and the voice box – affect 900 to 950 people here each year. If discovered and treated early, patients have an 80 per cent chance of surviving five years or more. If the cancer is diagnosed in the late stages, the survival rate drops to 20 per cent.

Professor Gopal Iyer, a surgical oncologist at NCCS, said head and neck cancers are a very big problem.

Previously, the cancers were seen largely in men aged 70 and above who were heavy smokers and drinkers. But doctors are now increasingly seeing patients in their 50s and 60s who are neither smokers nor drinkers, as well as more women.

This is a global phenomenon that doctors are unable to explain, said Prof Iyer.

About six years ago, Prof Iyer and Associate Professor Daniel Tan, an oncologist at NCCS, discovered a gene mutation that made about 3 per cent to 5 per cent of squamous cell carcinoma (SCC) head and neck cancers treatable with a lung cancer drug called Iressa.

SCC is a type of cancer that develops on the outer layer of the skin and certain parts of the body, such as the head and neck, as well as the lining of respiratory and digestive tracts. It accounts for about half of head and neck cancers.

In a 2015 trial, nine patients with advanced SCC with this mutation, each with a life expectancy of six to nine months, were treated with Iressa.

Five patients survived more than three years. Of this group, two are still alive today, one died of another cause, and two had a recurrence of the cancer, but could not be given the same treatment because they were no longer responding to it. The other four patients did not respond as well, although their tumours did shrink slightly.

The team did not know how the mutation worked, but it was significant enough for publication in the prestigious Nature Medicine journal, which also ran an editorial on the team’s discovery.

With its curiosity piqued, the team applied for research funding and received $1.5 million twice from the National Medical Research Council, in 2018 and 2022.

The team already knew that drugs like Iressa worked only on patients with tumours whose growth is driven by a mutation in the epidermal growth factor receptor (EGFR) gene. Although 90 per cent of the patients had that mutation, the drug was successful in only 3 per cent to 5 per cent of them.

With the funding, the team worked on identifying the exact factor that caused the cancers in the small group of patients to succumb to the drug.

Prof Iyer said: “When people look for biomarkers in blood, it’s like sieving through a river of junk, and trying to find gold.”

But luck was with the team. They discovered that the tumours that shrank released exosomes that carried a particular protein called isoform D.

Exosomes are tiny packages of genetic information, such as DNA, RNA and proteins, that are produced by all cells and which act as messengers between the cells.

The doctors discovered that by injecting exosomes containing the protein into the bloodstream, they are delivered to the tumours and absorbed by them, making the tumours more susceptible to the drug.

It is easy to “make tonnes of exosomes with the protein”, Prof Iyer said. The team makes them in small, 10-layer boxes in the laboratory and can produce 1.4 billion exosomes in 72 hours.

Currently, these are purely of research grade. For clinical trials, the exosomes must be of a quality that can be used in humans.

The team has approached the Bioprocessing Technology Institute, a national research institute funded by the Agency for Science, Technology and Research, to help produce the human-grade exosomes.

They have applied for grants to finance the exosome production and clinical trials.

Once they can produce clinical-grade exosomes and get clearance from the Health Sciences Authority for the clinical trials, they will start testing the treatment on 20 to 30 patients who have not responded to conventional treatment and have only months of life left.

The drug Iressa, which cost about $2,000 a month in the past, has been off-patent for some years and is now available at less than $100 for a month’s supply.

Prof Iyer said that if the treatment proves successful, it could each year potentially help 100 patients with head and neck cancers who have run out of viable treatment options.

It may also work on other EGFR-driven SCC, such as gastric, lung or breast cancers. Should that be the case, many more patients can be helped with this low-cost option.

The team’s work was published in the Developmental Cell journal in August. It has taken out a patent on the process.