Answers in Anomalies: Researchers at CUHK develop new strategies for early cancer detection

Every year, US$50 billion is spent globally on developing new cancer treatments and technologies. Despite the constant stream of advancements, the disease was still the second leading cause of death worldwide in 2018, claiming an estimated 9.6 million lives, according to the World Health Organisation. That’s equivalent to the entire population of Sweden.

In Hong Kong, around 30 per cent of all deaths in the city are from cancer, according to statistics compiled by the Hong Kong Cancer Registry. While cancer remains a top concern, local researchers in the medical and life science fields are continuously working to advance prevention techniques, enhance treatments, improve access to drugs, collect data, as well as further our collective understanding of how cancer cells mutate and proliferate.

As part of a global effort, Hong Kong’s top minds have been working with, and even outperforming, some of the most well-funded institutions in the field to tackle the complexities of cancer. Among them are Rossa Chiu, Dennis Lo and Allen Chan.

This team of chemical pathology professors and DNA specialists at the Chinese University of Hong Kong (CUHK) have been at the forefront of clinical research that has huge potential to reduce cancer mortality rates through early detection.

A life-saving screening

The Prince of Wales Hospital in Shatin is a warren; a maze of identical looking corridors, sanitised both in look and smell. This is where Chiu and her team have been developing a non-invasive technique called a liquid biopsy to detect early-stage nasopharyngeal cancer – a form of nose and throat cancer that’s rare amongst Westerners but common in Southern Chinese men.  In fact, it’s the most common cancer occurring in Hong Kong males aged 20 to 44 years.

The technique is much simpler than a traditional biopsy. Instead of extracting a tissue sample from the tumour using a large needle or an invasive surgery, a liquid biopsy requires a 10-millilitre blood sample. From there, researchers can test for DNA anomalies in plasma samples, identifying any possible fragment of DNA that points to the presence of nasopharyngeal cancer – even before it’s evident on a scan.

 As part of the landmark study, more than 20,000 ethnically Chinese men between 40 and 62 years of age underwent a simple blood test at the CUHK’s Department of Chemical Pathology between July 2013 and February 2016. By all accounts, the men seemed healthy, presenting no symptoms. But DNA markers in their blood told another story: 309 men showed potential factors for developing the disease. Of those, further testing revealed that 34 subjects had nasopharyngeal cancer, mostly stage 1 or 2.  

Early detection is critical when it comes to cancer diagnoses. Before the study, oncologists diagnosed 70 per cent of nasopharyngeal cases at stages 3 to 4 when patients present symptoms. But by that point, surgery, chemotherapy and radiation are less effective than they could have been.

So far, the results of the CUHK study suggest that those who have a liquid biopsy will have a 10 times better survival rate than those who don’t for this specific type of cancer. That’s because, with the screening, doctors caught 70 per cent of cases at stages 1 and 2, when treatments are most viable.

Ahead of the curve

Considered the first large-scale study of liquid biopsy as an early diagnostic screening tool, the team’s research was published in one of the world’s most prestigious medical journals, the New England Journal of Medicine, and was later included as one of the journal’s 10 most noteworthy articles of 2017.

In the midst of the study, in 2014, the three scientists established Cirina, a commercial company with labs in Hong Kong and San Francisco, to further develop blood-plasma tests and detect devastating diseases before symptoms emerge. The team remains at the forefront of early-detection research – way ahead of well-funded Silicon Valley companies that had been racing to develop the screening method.

“Silicon Valley can blow a billion dollars on this, but Hong Kong can actually beat them,” says Scott Edmunds, executive editor at Gigascience, the flagship publication of BGI, one of the world’s largest privately-owned genetics research companies. Based in Shenzhen, it provides cancer screening and testing services to doctors in Hong Kong. “I wouldn’t be surprised if they got the Nobel Prize [for their work],” he adds.

Edmunds is himself a former cancer researcher, who studied eye melanomas early on in his career. “[Grail, a health diagnostic company in Silicon Valley] had a billion dollars to spend on [liquid biopsy research] and [didn’t get as far]. [Meanwhile] Rossa, and a few other people here in this tiny little [operation]… they’ve been the first players in the world to do what Grail has been trying to do, on a complete shoestring,” he adds.

Aspiring to develop tools for early cancer detection, Grail has been funded by the likes of Amazon, Bill Gates, Bristol-Myers Squibb (an American pharmaceutical company), Illumina (a global genomics leader) and Tencent. The Cirina team’s groundbreaking study furthered Grail’s own objectives, and, in 2017, the two companies joined forces.

What makes Chiu and her team’s work all the more impressive, Edmunds says, is that the city’s current research and development funding per capita is equal to that of North African countries. Data from UNESCO shows that Hong Kong’s current spending on research and development is on par with Morocco and Tunisia. The difference, however, is that the city has a higher concentration of researchers per million people: 3,312 researchers per million people, versus 1,800 per million in Tunisia, and 1,020 in Morocco.   

“The [Hong Kong] government has made this big show that they’re doubling the [research and development] budget [from 0.73 to 1.5 per cent of GDP],” Edmunds laments, referring to a November 2018 announcement by Chief Executive Carrie Lam. By comparison, Singapore spends around 3 per cent per capita, while South Korea leads the region with 4.3 per cent of GDP per capita.

Valuable trials in Hong Kong

While relatively short on funding, the cancer research sector in Hong Kong has contributed valuable insights over the past few decades. “Personally, I think in terms of cancer management, Hong Kong does particularly well [when it comes to] its clinical trials,” says Chiu.

There are a few reasons for that. With Hong Kong’s high-density population, it’s easier for researchers to recruit a larger number of patients within a short timeframe. In addition, the city keeps thorough patient medical records, and the population is relatively homogenous in its genetic makeup. Genetic homogeneity usually makes a study more reliable and robust, because it means less variation to interfere with the study.

Variation, particularly when it comes to genetics, can strongly influence clinical studies. For example, someone from Spain won’t necessarily react in the same way to treatments as someone from China, and even cancer itself doesn’t present itself equally among people. That’s often the case with nasopharyngeal cancer.

In addition to an ideal demographic pool, seasoned medical researchers Chiu, Lo and Chan are pioneers in the field of plasmablood early detection tests. Prior to the liquid biopsy, Dr Lo was the first scientist to discover the presence of circulating fetal DNA in a pregnant mother’s blood. This made it possible to test for genetic conditions like Down Syndrome without inserting a needle into the womb. This non-invasive test is now employed widely around the world. 

They extrapolated this technique to cancer: “Researchers have realised that when a cancer grows, its cells will die and release its DNA into the blood,” says Chiu. “Imagine the blood is like a trash can of all the materials coming out of dying cells, we can now just take a blood sample and look for a glimpse of DNA abnormalities that might be suggestive of cancer.”

A shapeshifting disease

Despite the billions spent on cancer research and treatment globally, there is still no ‘cure’ for cancer. That’s because cancer is a difficult disease to treat, as it isn’t one disease. While the classic definition of cancer – the uncontrolled growth of cells in your body, caused by malfunctioning genes – still stands, it doesn’t really reflect the reality of it.

How a cancer starts and spreads can be as varied as the background of its patients. Why do genes start mutating? Why does one person who is exposed to a carcinogen (cancer-causing agent) develop cancer, while another does not? Every cancer manifests differently according, in part, to a person’s genetic profile.

“Even with the most powerful gene therapies targeting specific mutations, why do they only work for a year or a little over a year?” Chiu asks. “It’s because every single person’s cancer is a little bit different, so it’s very difficult to find a perfect match or exact treatment for every person.”

This variance is why the one-size-fits-all traditional radiation and chemotherapy aren’t always successful, why researchers are constantly looking for alternative treatments, and why there’s a caveat to even the positive results of the team’s liquid biopsy. While these researchers have invented a new method for early detection of nasopharyngeal cancer, other tests need to be developed for the early detection of other cancers.

It’s also too early to say whether it would be possible to detect any other forms of cancer this way. Looking ahead, the team’s lab will continue to conduct clinical trials with an aim to improve the accuracy of the test, reduce its cost and eventually roll it out to the public. Currently, the group is also examining the potential of liquid biopsies to detect other forms of cancer in early stages and its efficacy on other populations. “[I] can’t share too much detail about our plans,” says Chiu. “Suffice it to say, as a researcher, one should aim to achieve community use of the tests.”

Immunotherapy in Hong Kong

What if, instead of using radiation or chemicals to destroy cancer cells, you could train your immune system to fight off the disease? That’s the premise of immunotherapy. With theories dating to the late 1890s, the treatment regime essentially enables the immune system to identify and destroy cancer cells masquerading as healthy cells.

As scientists acquire new technologies and a deeper understanding of genetics, immunotherapy has emerged as an active area for researchers in recent years.

Currently, there are more than 40 new immunotherapy techniques being tested and developed worldwide, and one of the key researchers in the field is based in Hong Kong.

For over a decade, Clinical Associate Professor Dr Thomas Yau, at the University of Hong Kong, and his team have been running clinical trials on immunotherapy drugs at Queen Mary and Prince of Wales hospitals. The research focuses on terminally ill patients for whom traditional treatments like surgery, chemotherapy, and radiation have been minimally effective.

So far, only a third of these patients have responded to treatments. But when it works, the results can be remarkable: “We have some patients who enrolled in clinical trials more than five years ago,” says Yau. “The disease completely disappeared.”

To date, immunotherapy has proven most effective in late-stage melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. Without clinical trials such as Yau’s, it would be impossible to know if immunotherapy works.

“We’ve seen immunotherapy try to replace chemotherapy in some diseases like lung cancer, so I think in the recent five years we’ve seen a lot of progress,” says Yau. “As many drug companies are investing in immunotherapy, I think the progress will be [even more] rapid [moving forward].”

Incoming Support

Cancer doesn’t just affect a patient’s body; there’s a profound impact on the mind as well. Despite the mental toll, psychological care is rarely included as a key part of cancer treatment. This is where Hong Kong’s forthcoming Centre for Clinical Innovation and Discovery (CCID) and an Institute of Cancer Care (ICC) could make a difference for patients and caregivers.

Led by University of Hong Kong’s LKS Faculty of Medicine, the ambitious project will be the city’s first purpose-built cancer-specific research and service centre when it opens within Grantham Hospital in Wong Chuk Hang in 2024. While the CCID focuses on cutting-edge research, the ICC will focus on the psychosocial and psychological needs of patients, families and caregivers.

“Most patients are psychologically resilient. It’s just 15-20 per cent that are in persistent distress,” says Dr Wendy Lam, an associate professor at HKU Med who will head the ICC. Those most susceptible tend to be patients with pre-existing coping problems, maladaptive coping mechanisms, as well as those lacking social support from friends and family.

“Every cancer patient should have access to psychosocial care,” says Lam. “We see it as a human right.”