The following is an excerpt from a Think:Health episode that aired on Sunday 2 April 2017.
Listen online 107.3 2ser (audio length 12:19)
Host: Jake Morcom
Guest: Mary Bebawy, Associate Professor Pharmacy, UTS Graduate School of Health
START OF TRANSCRIPT
Mary: The problem with cancer is cancer spread, right.. once a cancer starts to invade foreign tissues then it becomes very difficult to treat..
Jake: This is Mary Bebawy, Mary is an Associate Professor of Pharmacy at the University of Technology Sydney.
Mary: Cancer is a disease of uncontrolled cell proliferation.. the cancer cells are just dividing uncontrollably and so you get an increased number of these cells within the body..
Jake: Mary’s research looks at how cancer cells can become resistant to multi-drug treatments.. Which essentially means when people with cancer become resistant to treatments like chemotherapy..
Jake: These sorts of resistances are a common problem… and aren’t restricted to just one type of cancer. The process of how we can form these resistances is a complicated one, but to understand exactly what Mary is doing in her research, we have to take a step back…. And we first have to look at vesicles..
Mary: If we break it down to simple terms, they’re like little bubbles.
Jake: Vesicles are naturally occurring in the body…
Mary: They are little power packets, they have potential to impact on physiology, on disease pathology and so on.
Jake: They are small structures within a cell that carry important proteins..
Mary: They were initially thought of in the late 60s as just remnants of cells that you found in a sample tube.. Initially they were identified as platelet dust, identified them in the context of platelets..
Jake: Vesicles are also involved in things like metabolism and the transporting of proteins…and what they’ll do is they’ll shed from their original cell and travel around the body..
Mary: And the vesicles are just a normal part of cellular turnover…
Jake: Why do cells shed themselves?
Mary: Just a normal cellular process, normal membrane turnover, it’s just a normal mechanism that cells have..
Jake: Where can you find vescicles in the body?
Mary: They're found surrounding the cells, mainly found systemically.. in blood and in biological fluids…
Jake: The medical world has known of vesicles for a while… but only recently have vesicles been linked to research around cancer..
Mary: The vesicles I study are cancer derived vesicles…
Mary: We’ve looked at vesicles from leukamia and they’re very small, they have an irregular surface… but if you looked at isolated from Milomoa patients..
Jake: Myeloma is a type of cancer of the bone..
Mary: They’re perfectly spherical… they look like little ping pong balls, they really vary depending on the cell of origin.
Jake: Looking at these vesicles gives Mary a greater insight into what the cancer is…
Mary: Provides us with a snapshot of the mother cell or the originating cancer cell.. We can look at the proteins on the surface of these vesicles or contained within the vesicle and we can look at the nucleic acids.. Its gives us a snapshot of what’s going on in the cancer cell.. So instead of accessing the tumour itself, we can take a blood test or sample and it provides us with this window into what’s going on with cancers, particularly those that are confined in inaccessible sites like the bone..
Jake: It also gives an insight into what the cancer is doing, and how it’s behaving..
Mary: so when you have a cancer patient and you look at their blood samples, they have a significantly higher number of cancer derived vesicles in their blood compared to healthy individuals.
Jake: How does it get to that point, what’s driving those to go up?
Mary: In the context of cancer its cell proliferation or cell division.. You’ve got a larger cellular burden in the context of the cancer cell, and as a result you’ve got more cells there, they’re shedding more vesicles.
Jake: However, there’s another major part to Mary’s research… and thats not just how vesicles can provide a greater insight into cancers, but also how vesicles can also play a role in the spread of cancer throughout the body.
Jake: But before we dissect that, you first need to understand how our immune cells work.
Jake: So the cells that we have that fight off things like cancer are these white blood cells called macrophages… which when you translate that from Greek, translates directly as ‘big eaters’.. And that’s what these macrophages they do.. They eat cells that are dangerous to
the body… like cancer cells..
Mary: These are sort of like sentinel gatekeepers.. They’re constantly monitoring the tissue environment for foreign cells or foreign particles… normally their role is they were to encounter these foreign cells, they’d engulf them and destroy them.. And this retains the integrity of our tissues..
Jake: But cancerous cells pose a number of problems for our macrophages... In this situation, When a cancerous cell forms in the body it does two things - one a cancer cell will continually divide causing more and more cancer cells in the body which creates a problem, but the second thing has to do with vesicles.
Jake: These vesicles will shed from the cancer cell, and then do something crazy.
Mary: these vesicles somehow functionally incapacitate these macrophages… they can’t engluf, they can’t move towards the foreign cell..
Jake: They paralyse them! By doing this, the macrophage is stuck… it’s frozen, and can’t eat up other bad cells to protect the tissue it looks after.
Jake: So when another cancer cell comes along, and sees this incapacitated macrophage…
Mary: Once the cancer cell approaches this immune cell in the context of the spread…
Jake: The roles switch!
Mary: Has the capacity to then destroy that macrophage by swallowing it up.
[music]
Jake: So there’s another part to this.
Jake: The vesicles which are shedding themselves from cancer cells and then are paralysing the good white blood cells, the macrophages, the vesicles that have this paralysing ability are only coming from cancer cells that are multidrug resistant.
Jake: And so you know, multidrug means there are multiple drugs or things used in certain treatments.
Jake: Now not all cancer cells are resistant to drugs or treatments - some cancer cells do
respond, meaning for example the chemotherapy works and it’s able to completely get rid of the dangerous cancer cells.
Jake: But the fact that some of these vesicles are coming from multidrug resistant cancer cells is important to note - and that’s because these resistances mean people don’t
respond to treatments, and they physically can’t get better.
Mary: This is a huge problem in the context of combination chemotherapy because treatment fails.. And the mechanism, the primary mechanism for multidrug resistance is the cancer cell overproduces a particular protein on the surface and it acts as a miniature pump.. And
when a drug tries to enter the cell it interacts with this protein and the protein essentially pumps it out from the surface, preventing the drug from penetrating the cell… and so the cell survives, it’s not being exposed to chemotherapy agents.
Jake: The really sinister thing about cancer, and also the really fascinating thing, is that cancerous are utilising what’s already in the body to spread itself.. Mary says, that cancer hijacks the body.
Mary: These proteins that are protecting cancer cells from chemotherapy insults… you would call it an insult.. Are also proteins that are required for normal physiology… it’s just the cancer cell has hijacked these mechanisms and overproduced this protein for its own
survival…
Mary: So these proteins play a very important role in the brain, in the gut, in what we’ve referred to as pharmological barriers… and these barriers it’s very difficult for drugs to cross into.. These are designed to protect vital organs..
Mary: These pumps normally line the brain and comprise a barrier in the brain… but also because of these proteins that protect the brain from drug uptake, they sit there and they will pump drugs back out and prevent it from entering the brain…
Mary: So these are normal physiological mechanisms that we have, but the cancer cells hijack them, overproduce them to aid their own survival.
Jake: What is the research that you’re doing on this unto this area to look at tackling these issues with multi drug resistances that develop in the body?
Mary: I’ve got a large program going in my lab and we’re looking at a number of things – we’re looking at developing new drugs that can circumvent or prevent multidrug resistance so new molecules that can be combined with standard chemo therapeutics that can try and tackle this problem. So we’ve got some drug discovery going on.
We also have a lot of cell biology going on, with a focus on extra cellular vesicles. How vesicles occur, so the mechanism for vesiculation, in cancer cells compared to normal cells and that’s very important for us to know because if we can define a specific pathway for vesiculation in a cancer cell that’s different to a normal cell we can selectively target that pathway in a cancer cell, while retaining the normal vesiculation in healthy, normal cells.
Jake: And what’s that pathway?
Mary: We’re sill looking at that. These are cellular pathways, so we’re looking at the different proteins within the cell that are involved, different enzymes that are involved in vesiculation. We’re really refining that pathway now, and once we do that we’ll be able to target parts of that pathway and stop vesiculation in malignant cells.
[Music plays]
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