Associate Professor Jason Lee:

Hi.

Clare Blake:

Where is the pancreas and what does it do?

Associate Professor Jason Lee:

All right. So, the pancreas is a digestive organ in a sense that it is actually behind the ribcage, just behind the stomach. So that allows gastric juices to come out, and helps to digest proteins, and carbohydrates and sugars. Some people actually do find out that there’s something wrong with the pancreas when they don’t digest food properly. A crucial organ that controls how you digest, and obviously digesting is really important for absorbing energy and nutrients.

Clare Blake:

How do you know if you’re not digesting food properly?

Associate Professor Jason Lee:

Well, I guess you might have some bloating in your stomach. There are times that you don’t go to the toilet for a few days, even if you’re eating well. Obviously, you’ll feel very discomforted by the stomach full of food still there. And there are lots of other reasons why you would actually have that condition, so people don’t really think that you’ll have something wrong with the function. It’s crucial that if you do know some discomfort and there are some symptoms that you might suspect, you should really go and get that checked out by a doctor.

Clare Blake:

It’s found late, but how is that normally happening?

Associate Professor Jason Lee:

There are some times when people are suddenly losing weight. In most cases, patients actually do go into the hospital and go through ultrasound, very invasive MRI. MRI is actually quite expensive, and also takes quite a lot of time. For example, for a mammogram for breast cancer, is actually less invasive and there are lots of centres where you can actually get things tested, whereas the MRI or ultrasound, you need to actually be in a big setting. One of the projects that we are trying to develop at the moment is to use blood samples. Patients can actually go into nearby clinics or pathology clinics that allow you to take blood, and this will give you some ideas as to whether you have pancreatic cancer or not.

Clare Blake:

This is where this recently identified molecule comes into play, and you think that this could really change the game and it could be identified in a very simple blood test.

Associate Professor Jason Lee:

Oh, yes. I’m really excited about the newly-identified class of RNA molecules called circular RNAs. Not many people thought that RNA could be a good candidate for early detection, because RNA being very fragile, and it breaks down so easily that people never thought of using them for biomarker development — liquid biopsies such as blood, saliva, sweat, and urine, for example. But this circular RNA, them being circular allows them to be very stable.

Clare Blake:

When you say it’s stable, how does that mean it’s good for a blood test?

Associate Professor Jason Lee:

Right. Stability means, standard RNA is stable for maybe minutes or half an hour at the maximum, but these circular RNAs can be in the blood for hours and days. I’m sure a lot of people have actually heard about the COVID vaccine.

Some of the COVID vaccine need to be transported in really cold, -70 degrees and so on. Yeah, that is directly related to the stability of the mRNA. If they’re just in room temperature, they break down. The circular RNA being stable means that you can actually just take the blood from patients in room temperature, not necessarily having to store them or transport them in really low temperatures, which is much easier for diagnostic labs to send samples and get them tested.

Clare Blake:

Much more cost-effective.

Associate Professor Jason Lee:

Definitely.

Clare Blake:

How would they help us diagnose pancreatic cancer?

Associate Professor Jason Lee:

One of the things that we’ve been focusing is to study blood samples from pancreatic cancer patients, as well as healthy subjects. We know that tumour cells change themselves, and this allows tumour cells to actually produce more or less of specific sets of circular RNAs. I guess as a biomarker or test candidate, we want to find something that is highly expressed in blood, that is actually derived from the pancreatic cancer cells. What we want to find out now is that whether these circular RNAs that are produced from the pancreatic cancer cells exist in the blood.

Clare Blake:

Could it be included in a simple battery of blood tests or is it a very unique type of blood test?

Associate Professor Jason Lee:

It would be my hope to have this test included in the battery of tests that patients actually do get tested for. But at the moment, circular RNA being a special class, requires a special method to be able to actually detect them. My hope is that perhaps in the future, that the technology would be advanced enough so that we could actually include them in other common tests that patients actually do get tested for.

Clare Blake:

Amazing. How much earlier would we be able to detect pancreatic cancer?

Associate Professor Jason Lee:

What we understand from pancreatic cancer incidents is the fact that it’ll be difficult for us to implement this test as a screening program, because the number of patients that would find pancreatic cancer will be so low compared to other cancer types, the test won’t be developed by companies who need to actually cover the cost.

Clare Blake:

So you’d be looking at patients with a higher risk. And how do you establish that?

Associate Professor Jason Lee:

Right now, we’re going to take the first steps in looking at blood samples from patients that suffer severe pancreatic cancer, and then we are going to test those blood samples from patients that were just diagnosed, at a relatively early stage, and compare the levels of circular RNAs to healthy subjects. So I guess the question is, how early can we actually detect them? Detecting pancreatic cancer at a metastatic stage, where the cancer cells have spread other organs is just too late, and that’s no better than other detection methods currently used in the clinic. So what we are trying to do is go from where a patient has a very aggressive-stage pancreatic cancer, and then move towards the earlier and earlier stages so that we can actually increase the sensitivity and that will allow us to have confidence that what we detect is actually real. One of the problems that a lot of these tests will have is false positives. You really don’t want to inform the patient, saying that, “Oh, you have pancreatic cancer,” when it’s really not. What we need to develop is lots of controls and lots of repetitions that allow us to actually have a very conclusive test result.

Clare Blake:

Pancreatic cancer has a very low survival rate, doesn’t it?

Associate Professor Jason Lee:

Oh, definitely. It’s a devastating disease in the sense that five-year survival of these patients with pancreatic cancer is less than 10 per cent. If you detect cancer early, you may be able to actually surgically remove the tumour and also stop the tumour from spreading to other organs, and gives chemotherapy or other therapies, that are now available, a better chance to be more efficient.

Clare Blake:

Where does pancreatic cancer normally travel to?

Associate Professor Jason Lee:

Everywhere, really. To the lung, liver, even to the brain. Vital organs are affected by pancreatic cancer.

Clare Blake:

Is there any chance that this blood test might have implications for other types of cancers?

Associate Professor Jason Lee:

Oh, that’s a really good question and a comment, because what we’ve been doing in the laboratory is to not only just focus on pancreatic cancer, but also ovarian cancer as well. Often, they are diagnosed at a really late stage. And it’s another cancer type that if you detect ovarian cancer early, the survival increases drastically, up to 90 per cent for overall survival in five years. So, currently, we have another research grant to work on ovarian cancer, which is supported by the Ovarian Cancer Research Foundation. I’m really grateful for that. Similar to what we are doing with the pancreatic cancer program, we are now looking at early detection from those patients diagnosed at early stage, but also at a later stage. Additionally, one of the things that we can actually do in ovarian cancer is that some of these patients are treated with therapies and the cancer goes away, that period where a patient thinks the cancer is not recurring but they’re constantly in fear whether the ovarian cancer will actually come back. And this is one of the things that we can actually do right now, that those patients that are in remission, we can take some of their blood to monitor whether the cancer cells actually are found in the blood, and allow them to have peace of mind that it’s not coming back.

Clare Blake:

Well, that’s extraordinary. I know that you have some funding to go on with your pancreatic cancer study from PanKind. There is a big leap now between where you are and getting it into a clinical setting, but you’re not leaving it there. You have other promising research looking at targeting a particular protein that makes the cancer cells very aggressive.

Associate Professor Jason Lee:

Yes, I have long been working in the field called epigenetics. This field is actually trying to understand how genes are regulated or controlled by factors that don’t involve DNA. A lot of people think, “Oh, you have mutation. You have this gene and you have those genes. Now you’ve lost that gene.”

But we are talking about things then that can affect gene expression in other ways. Lifestyle or diet, or exercise, can affect the expression of certain genes, and there’ve been quite a lot of epidemiological studies that have linked gene expression to epigenetic changes. Pretty much everything that can change the expression of a gene without involving the changes in the DNA, and you can think of that as an epigenetic. So whether you’re in a stressed environment, or whether you’re in a hot environment or cold environment can affect gene expression.

And one thing that we’ve actually found is that there’s this protein that controls these epigenetic changes — we found that this protein that participates in epigenetic modification are found in really high levels in a lot of cancer cells. What we are trying to do is [see] whether we could develop a drug that can stop the function of this protein. And some preliminary data suggests that we can stop cancer cells growing. We can make these cancer cells stop spreading to other organs, as well as to make other therapies more effective. In the laboratory, we have actually tested in combination with chemotherapy as well as endocrine therapy for breast cancer patients that become resistant to these therapies. We have data suggesting that it can either make other therapies more efficient; or sometimes, when patients become resistant to these therapies, we can use this novel drug and we just don’t need to actually combine them at all. We can overcome their resistance mechanism to allow cancer cells to die.

Clare Blake:

Ever since I’ve met you, Jason, you’ve always been really dedicated and frustrated by those aggressive cancers like triple-negative breast cancer, ovarian and pancreatic cancer, and you want to level the playing field.

Associate Professor Jason Lee:

Oh, definitely. I mean, one of the reasons why I’ve been so focused in treating these aggressive cancers is actually from talking to the patients. So there were a number of occasions where QIMR Berghofer Medical Research Institute organised consumer meetings, and whenever I talk to those patients that are affected by cancer, it’s really about controlling the cancer to not come back. We’re not the only ones that are trying this approach. There are many clinicians and scientists around the world that have actually tested this hypothesis, and things are actually becoming reality. There are lots of n-of-1 clinical trials. We’re not grouping hundreds and hundreds of patients in clinical trials, but they are focusing on one patient as a clinical trial, because the cancer type, their genetic makeup, or their responsiveness to drug is all different from one individual to another.

I think that the technology and the approach that people are taking will actually allow precision medicine or personalised medicine to actually become reality. Cancer patients often find themselves not benefiting from treatment from the get-go. Others show some response initially, but become resistant. Therefore, we want to be able to identify patients that would develop resistance, or whether they’re not going to benefit from the drug initially, so that we don’t give the drug to anyone, but we would give the drug to those patients that would benefit from it. The other would be early detection. Any sort of of early detection using a very simple blood test, would benefit all cancer patients.

Clare Blake:

And it would level the playing field.

Associate Professor Jason Lee:

Oh, definitely. A lot of research has actually been focusing on some category of cancers, but I think to some extent pancreatic and ovarian cancer have been neglected. Even if you go to the clinic, for example, there are probably about five to eight nurses looking after breast cancer patients, but there’s only one for a pancreatic cancer patient in a clinic. So there needs to be awareness of how much funding needs to be provided for patient care. Not only for research, but also for patient care as well.

Clare Blake:

You do have some support to keep that research going for now, but there is a giant leap from here in the lab to the clinical space, where you need a lot more money.

Associate Professor Jason Lee:

Yes, definitely. We need lots of money for funding. Huge thank you to PanKind, as well as a donation from Jacqueline Pascal. Without that money, we would not have been able to continue pancreatic cancer research.

It’s not just the funding. But also, we need clinical samples and blood samples for our research to progress. So if you’d like to actually donate your blood as a healthy subject or a patient, we welcome your participation into our research project.

Clare Blake:

And if you would like to help or you’d like to find out more about Associate Professor Jason Lee, his team, and their great work go to qimrberghofer.edu.au. Thanks, and good luck, Jason.

Associate Professor Jason Lee:

Thank you. Pleasure.

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