Podcast: Exploring Liver Cancer Research with Associate Professor Naiyang Fu

October 31, 2023

LiverWELL · Liver Cancer Research with Associate Professor Naiyang Fu


In this podcast, Paulette Trevena from LiverWELL speaks with Associate Professor Naiyang Fu, the first recipient of the LiverWELL Mid Career Research Fellowship.

Associate Professor Fu delves into his fascinating research at WEHI on liver cancer detection, and the importance of a gene which could be beneficial in liver cancer diagnosis and treatment.

PT: Welcome to another podcast from LiverWELL.
In this podcast I’m speaking with Associate Professor Naiyang Fu, who is the recipient of the first LiverWELL Mid Career Research Fellowship. Naiyang has been working in liver cancer research for seven years, in Singapore and Australia. His research here is taking place at WEHI formerly known as the Walter and Eliza Hall Institute of Medical Research in Melbourne.  Naiyang, welcome.

NF: Thank you.

PT: So liver cancer is the cause of a huge health burden in our community, in the health system and in our future economy. Why did you choose to work in liver cancer research?

NF: I used to work on breast cancer. But in 2016, when I set up my own lab, I literally realised a lot of knowledge I learned from breast cancer studies can be used for liver cancer. And liver cancer, as you say, is a huge burden for a community. By now there’s no really good target for liver cancer treatment. That’s why I was really interested to start my lab in 2016, to work on liver cancer. From that, in the past seven years, the main focus of my lab is on liver cancer.

PT: So people might not realize that that liver cancer is the third leading cause of cancer-related death globally. Is this rate still increasing?

NF: Yes. While the mortality of most cancer types has declined in the last 10 or 20 years, but both cases and deaths caused by liver cancer has substantially increased. One of the main reasons is we really can’t diagnose liver cancer at early stage, and we don’t have a molecular marker we can target to achieve a good efficacy in liver cancer. That’s why the chances are still increased. In 2020, close to one million people around the world died because of liver cancer.

PT: So is liver cancer increasing because of things like fatty liver disease, despite hepatitis B vaccine and hepatitis C treatment?

NF: Yeah. Because the HBV vaccine is so powerful, people think maybe liver cancer is going to drop down. But unfortunately, because of diabetes and fatty liver, because of eating too much every day, with drinking alcohol, that the liver cancer incidence is increasing, and probably getting worse and worse in the next 10 or 20 years.

PT: So why has it been so difficult to achieve early detection of liver cancer?

NF: That’s a very interesting question because you know, liver is that internal organ not like other organs, where you can see clearly that tumour development. And the other thing is, most of the time there’s no sign or symptom during the early stage of liver cancer development. That’s why it’s so difficult to detect liver cancer at an early stage. And that’s why my lab is so interested to develop a new approach that can be used for early detection of liver cancer.

PT: So why is there a high rate of metastasis and recurrence for liver cancer?

That one main reason is, you know, a lot of blood vessels in the liver. Liver is one of the organs fully filled with blood vessel because the nutrients from the small intestine have to go to the liver. Many, many small blood vessels in the liver. For cancer metastasis, cancer cells have to go to the blood vessel, and then they can migrate to other places. And because of so many blood vessels in the liver, it does make the liver become one of the organs, where once you get cancer, it’s very easy to spread out and migrate to other organs.

PT: Okay, so tell us more about your research.

NF: So maybe I’ll just focus on this project. We really focused on a new gene we identified a couple of years back. We found this gene is very, very interesting. This gene is normally not expressed in the hepatocyte. Hepatocyte is the cell becoming transformed and driving the liver cancer development. But very interesting – when we develop a mouse or animal model to look at the early stage or early event of liver cancer development, one of the genes we really feel is remarkable is this gene. It is very robust (turned on in liver cancer). In a normal cell, you don’t have this gene expressed; it’s completely silent. But once the cell becomes transformed, it will start to express this gene. That’s why we started to be interested in this gene and try to develop a new approach based on this gene, for liver cancer diagnosis and treatment.

PT: So this gene is highly expressed in liver cancer, how was the gene discovered?

NF: This is kind of “by accident”, I have to say, because a few years back when, when I worked on breast cancer, that’s one gene we are interested in for a long time, this gene labels quiescent stem cell. So very surprisingly, when we look at mouse models for some sort of liver cancer, and we find this gene is highly, highly expressed. And because we have some very unique molecular tools for this gene that nobody else in this world has. So based on our unique tools, we identified this gene is really a good marker for HCC.

PT: So does it play a role in development of the cancer? Is it a marker for cancer?

NF: This is really a good question, again. This gene is not just like a marker for HCC, in fact, we use a very cutting edge strategy, we try to use a method to knock out this gene and then look at how the tumour progresses. Surprisingly, we find once this gene is knocked out, the tumour almost cannot form in the in the liver any more. So this means this gene is not just a marker for the HCC, but it also plays a very important role for the tumour growth in the liver.

PT: And is this in all cancers or only in the liver?

NF: Actually, well, after we identified this gene, we go back to search literature. And we find actually, that this gene is very interesting – it’s not just unique for HCC, of course, this gene is expressed in some other tissues. So we have to say this gene is not just a marker only expressed in the HCC. If we learn anything about this gene from HCC, in future published knowledge can apply to other cancer types. This gene also can be a target for the treatment of other cancer.

PT: Excellent. So it might have bigger implications in the world of cancer research. That’s wonderful. And does it affect the primary cancer as well as the metastases?

NF: That’s for sure, we have very strong data. There’s an assay called cell invasion. It is kind of an in-vitro culture system mimicking the cancer metastasis in the body. So we use this assay, we find if we knock out this gene, the cell is no longer able to invade through the tissue. That means if you put back into the body the cancer without this gene that it likely cannot metastasise anymore. As I mentioned previously, this gene is extremely critical for the tumour growth, because if you knock out this gene, the tumour almost cannot form. So it affects both tumour growth and metastasis.

PT: Right. So we hear the word biomarker used a lot in cancer research, what does a biomarker actually mean?

NF: Yeah, biomarker is kind of a naturally occurring molecule. It can be used to identify a particular pathological or physiological process or disease, then we will call this as a marker for a particular disease or process. In this project, we will not just look for a marker for HCC, we actually want to look for a marker the blood of the patient. We hope we can by testing the expression of this gene in the blood, we can use this as a method to identify whether that patient might be able to develop HCC.

PT: Do you think that sort of testing could be done widely as a test for cancer or would only be for patients who’ve already been identified with cancer?

NF: Yeah, so we probably have to combine this gene with other markers together for HCC or for liver cancer. But if we just look at this gene at this moment, we can’t say this is a unique marker for liver cancer, we still need to do a lot more study in the future.

PT: So Naiyang, your project finishes in 2028. Is that right?

NF: Yes, yes.

PT: And do you think this is likely to progress to trials -would that sort of thing be well into the future?

NF: Yeah, that’s our dream, for sure. We really try to conduct our translational research in this project. And we really aim to develop a novel strategy for diagnosis and therapy of a subset of liver cancer patients. So by the time of this project finishing in 2028, we really hope we will be strongly positioned to initiate a clinical trial to test the feasibility and efficacy of the strategy developed in this project for liver cancer. We have a plan. By the time this project is finished, we hope to initiate a test for a large cohort of patients, not just in Australia, we’ll probably collaborate with clinicians in China and in Singapore also. We really want to build up a new approach for diagnosis and test the efficacy of whether this gene is a good marker for treatment of liver cancer.

PT: Fantastic. I’m sure there’ll be a lot of people who’d be very interested to see its outcome. Are there many researchers working in this field globally, or is this unique to Australia and WEHI at the moment?

NF: Oh, according to our knowledge, probably our team is the only team at this moment trying to conduct systematically, a study from preclinical models to patient samples. We really try to engage many clinicians to participate in our project. We really hope by the end, because we are really in a unique position here, we have many unique tools, including monoclonal antibody and animal model. And we have already engaged some experts in liver cancer study, some excellent clinicians. So I think,  based our knowledge, maybe still some have some other groups on there, but we really believe we are the only ones trying to conduct a study in a really systematic way to understand how this gene is regulating liver cancer. And how can we use this knowledge we develop to target this gene, to give us a new strategy for treatment of liver cancer as also as a diagnosis method for liver cancer.

PT: That’s fantastic. Sounds really promising. We look forward to hearing more about this research in the future and one day perhaps seeing it in use for patients.

NF: Wonderful. We really wish by the end of this project, we really can move forward to work getting very close to initial clinical trials and really try to benefit a huge proportion of patients who have high expression of this gene. That’s our dream.

PT: Wonderful! Associate Professor Naiyang Fu, thank you so much for your time and for explaining your liver cancer research for us. I know our audience will be really keen to hear about it.

NF: Thank you so much.

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