A constant gardener
The liver is among the most important cogs in the body’s machinery, which in turn makes cancer at this site more dangerous. Liver cancer is growing more common worldwide, and is the third highest fatal cancer in Hong Kong. As a particularly aggressive cancer, it is usually detected at later stages, when surgery is no longer viable, and with high recurrence rates and resistance to chemotherapy, the prognosis is often grim. Other modalities of diagnosis and treatment are vitally needed, opening up opportunities for research which have made promising advances in treatment and survival.
To Dr Irene Ng, liver cancer is like a particularly stubborn weed. “It grows fast, and you can’t see how deep its roots are. You can throw weed killer on it, but it grows back; you can dig and get some of the roots, but you don’t know how much you’ve missed, and in the meantime it’s taking over your garden. So take a minute, think strategically and identify what makes the root tick—that’s a novel target.”
Having identifying CSCs as a possible such target, Ng is currently investigating antibodies and molecularly targeted drugs that can go straight to the root of the issue, suppressing CSC’s ability to trigger tumour growth and resistance to conventional chemotherapy techniques for now.
Finding the target
Key to this is understanding the mechanism of tumour recurrence and chemoresistance, which is where Ng’s research comes in. Cancer stem cells (CSCs) are believed to be responsible for tumour initiation and growth, and are more resistant to conventional chemotherapy than more mature tumour cells, and this may make eradication through current treatment more difficult.
Ng’s lab was the first to identify a subset of CSCs responsible for the rapid growth and chemoresistance of liver cancer, finding that patients whose tumours had higher CD24+ expression also had a higher risk of tumour recurrence and metastasis, with lower survival rates. They also pinpointed CD24+ as the mechanism which maintains self-renewal of CSCs and tumour formation through activation of STAT3 signals, shifting research to ways of inhibiting these signals for better treatment options.
Working with clinicians
The question of how to solve a problem like cancer blurs the lines between science and medical specialties perhaps like no other. Researchers and pathologists in Ng’s lab and surgeons come together, and finding ways to complement each other’s research is easy given the translational nature of the work: finding a novel treatment target in liver cancer could give valuable insights into other cancers.
“Our research is always tied to clinical realities, whether validating our findings in patient samples, or taking things back to the lab to answer questions. In that way, my lab is a good bridge for that essential communication” she says. Building on this point, she disagrees with the idea that research is largely static or theoretical, especially given the increased collaboration between different scientific fields, citing the need to be aware of different clinical realities, other research, and new chemistry, just to name a few factors.
Novel gene targets have attracted the attention of international pharmaceutical companies, many of which are reaching out to universities for translational research on ideas, technology, and preliminary plans for better patient care.
Before clinical trials, molecularly targeted medicine needs pre-clinical testing to determine responsiveness and more options for personalised medicine, a trend growing simultaneously alongside targeted research. It also coincides with public health questions, as Ng sees in her work, with the increase in non-alcoholism related liver cancer and changing risk factors.
“With universal newborn vaccinations for hepatitis B, that disease is on the decline, but it’s an important indicator for liver cancer. At the same time, metabolic syndromes such as obesity and diabetes are becoming more prevalent, so what we look for, what we consider risk factors, and how we treat disease is also changing,” she says.
Looking forward, Ng is enthusiastic about the trend towards more translational research, as the mechanisms of why cancer is born needs to be better understood for new treatment options and answer important biomedical questions. “Researchers and clinicians working together gives us newer and more powerful tools. With people living longer and cancer on the rise, we need better diagnostics and treatment.” Both research and science as a whole are becoming increasingly more interdisciplinary and targeted, and Ng considers women to be a crucial driving force.
“We are more in need than ever of fresh eyes and bright minds,” she says, “We have different questions we want to solve, but women are by no means weaker, and in my experience we bring unique advantages to research.” Half of Ng’s lab and more than 40 percent of medical students at the University of Hong Kong are female, and Ng says her best advice is for these young scientists to not be discouraged by the difficulties still present. “We are our best advocates, in science, for our female patients, and for societal attitudes. I tell all my students to ask the difficult questions, not take no for an answer. The future depends on keeping that passion alive.”
Dr Irene Ng received her medical (MBBS) degree from the University of Hong Kong in 1980, Doctor of Medicine in 1994, and her PhD in 2005, winning Senior Medical Research Fellowships from the Croucher Foundation in 2005 and 2013. Dr Ng is currently the Loke Yew Professor of Pathology and Department Chair at The University of Hong Kong, and also serves as the Director of the State Key Laboratory for Liver Research at the University. She is ranked in the top 1% in the ISI list of most cited scientists in clinical medicine.
To view Dr Ng's personal Croucher profile, please click here.