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The making of a living ovarian cancer biobank

Lilly Matson
by Lilly Matson | Analysis

20 February 2020

19 comments 19 comments

Stephen Taylor's Lab, Manchester, Microscope

It’s an ordinarily overcast day, but the artificial lights of the lab radiate a crude brightness for Professor Stephen Taylor and his team.

The room is bustling and busy. Scientific equipment and bottles filled with striking liquids are spread across the work benches, and there’s a machine in the corner that seems to be sucking up a solution from one location and decanting it elsewhere.

There’s a faint hum of machinery and a distinct smell of antiseptic hangs in the air.

Here, in this compact, energetic lab in a southerly suburb of Manchester, a group of researchers are nurturing a collection of living ovarian tumours.

“A biobank is just a bank of tissue, that’s all it is,” says Dr Rob Morgan, a medical oncologist working on the project. The term was first used in the 90s and essentially refers to an archive of human material used for medical research.

The samples can originate from various places in our body, from skin cells and organ tissue, to blood and urine samples. Collections like this are vital for understanding the biology and genetics of a particular group of cells.

But the problem with most tissue biobanks is that, in order to create them, scientists take samples and either preserve them by dropping the sample in a solution of formaldehyde or freeze them at minus 80 degrees.

Both methods fix and kill the samples, “so there is a bit of somebody’s tumour, that is technically dead, just sitting in a freezer,” Morgan explains.

But their biobank is different. It may not be breathing as we know it. But it is alive, and it is growing. 

Stephen Taylor's lab Manchester Institute, media solutions

A selection of the liquids the team uses to make up the magical media which allows ovarian cancer cells to grow

So how do the cells go from growing inside someone’s body, to growing in their lab?

It’s a long process, or ‘pipeline’ as Morgan calls it, that begins with gathering samples from patients at the Christie hospital, just over the road.

Women with ovarian cancer often develop a build-up of fluid in the abdomen, known as ascites. It’s a particularly uncomfortable symptom of advanced cancer, which doctors drain to help relieve the swelling.

It turns out this fluid is choc-a-bloc with cancer cells, so the majority of the team’s samples come from these procedures.

The pipeline begins with a team of 3 or 4, who work for the Manchester Cancer Research Centre (MCRC) Biobank, a larger biobank that collects samples from people with cancer across the Greater Manchester area.

The MCRC biobank technicians are responsible for collecting the samples. So, when a woman comes into the clinic and presents with a swollen stomach, they’ll explain the biobank’s work and give her the opportunity to consent to a sample being used for research.

“Not every patient does agree, most patients do, but not everyone does. It’s an interesting conversation, a challenging conversation,” Morgan remarks.

If someone is happy to donate a sample, the MCRC technicians will stay with them during the procedure, then carry the sample over the road and drop it off to the lab.

The lab is normally given around 1 litre of whatever is drained, but anything up to an astonishing 10 litres of fluid can be drained from a single ascites.

Being so close to the hospital is a real bonus for the team – cancer cells can be in someone’s stomach in the morning, and in the lab by teatime.

The team works with solid tumour samples too, which will be collected directly from surgery. “That takes a little bit more coordination,” Morgan explains. This is a truly collaborative project. The most recent paper, published in the journal Nature Communications, is co-authored by two gynaecological surgeons, a pathologist and a cancer doctor, to name just a few.  

Stephen Taylor's lab Manchester Institute, Louisa pipetting

Louisa Nelson works with the tumour samples at the University of Manchester

When samples arrive in the lab, they’re passed onto Dr Louisa Nelson, the architect of the living biobank.

Nelson joined the team 5 years ago, when they were still figuring out how to get the cells to grow. And now it seems like they won’t stop. “So far they’ve all carried on growing for months and months and months. We haven’t actually got to the point where they have stopped.”

The flourishing biobank is thanks to a research team in Florida who first created the magical media that could get ovarian cancer cells to divide.

It’s Nelson’s job to look after the cells, which Morgan says she does diligently. “What Louisa does is she keeps the tumour going, and that’s why it’s more than just a biobank. There’s a lot of care and attention.”

When they first arrive in the lab, Nelson houses the cells in narrow, flat flasks filled with fluorescent orange media, stacked neatly on top of each other and kept at 5% oxygen, just like they would in the abdomen.

Once they start growing, she begins to separate the tumour cells from all the other cells in the sample.

And then the real analysis can begin. 

Stephen Taylor's lab Manchester Institute, incubator

Nelson takes tumour samples out of the incubator, where they are kept at 5% oxygen

Since the biobank has been established, the team have analysed the ovarian cancer cells living and dividing in acute detail. And what they have uncovered is a remarkable level of differences between ovarian cancers, with no two cancers genetically looking the same.

Nelson explains that when the ascites samples are dropped off to her, they already look completely different from one another. You might expect them be to straw coloured, but they have received fluid that ranges from ‘pink, to yellow, to purple’. It ultimately depends what cells and molecules are floating in the fluid.

Although scientists already knew that ovarian cancer has a degree of rearrangement in its DNA, Taylor explained how the chaos they witnessed at a chromosomal level is really quite unprecedented. “You have got to have an appreciation of the problem before you can start to tackle it and I think what we would say is that we haven’t really appreciated the scale of the problem until now.”

That’s because most experiments have relied on cancer cells that have been grown in the lab for decades, rather than cells taken from fresher samples.

The most used cell line of all time, the immortal HeLa cell line, was established using cervical cancer cells from the young American woman Henrietta Lacks. The cells were taken on the 8th of February 1951, the same year that Churchill was re-elected as Prime minister.

Nelson explains how with these cells, “because they’ve been growing for so long, the stronger, fitter and faster growing cells will dominate that culture,” so they all end up looking the same.

And here lies the key to their findings. “It is kind of like a bespoke, patient specific, tumour cell for that patient,” explains Morgan. “That is the key really, from a clinician’s point of view. What we’re all striving for is a perfect model of the patient that we’re sitting in front of.” And it is this uniqueness to their work that has exposed new findings about ovarian cancer.

Morgan says the team are trying to replicate each tumour’s environment as accurately as possible in the lab. This means that the tumours in the biobank should mirror those from the patient.

And, for some, the team go one step further – collecting tumour cells from fluid samples taken at different times. By accumulating samples throughout the lifespan of the tumour, they can follow changes as someone’s cancer progresses, and when they relapse. In one case, the have collected nine samples from a single patient.

But there are challenges with the biobank too. The issue, Taylor explains, is that because they’re dealing with samples from people with more advanced cancer, they don’t yet understand what’s driving this instability. Is it there in the early stages of the cancer, or does it develop later, perhaps as a response to treatment?

However it develops, Taylor believes this instability could be harnessed to develop new treatment options. “We know that the chromosome instability can drive drug resistance, but we also know that chromosome instability can be exploited to develop new therapies,” says Taylor.

And that is exactly what the team are beginning looking at now.

Stephen Taylor's lab, Manchester, testing drug sensitivity

Testing the drug sensitivity of the tumour samples

While the team is continuing to study how the tumour cells respond to a variety of drugs, comparing these results to how patients respond to treatments in the clinic, there are big plans for the future of the biobank.

“What we want to do is build this as a resource, not just for my team but also for the community,” explains Taylor.

The next step will be attempting to combine the tumour cells back with all the other cells as part of their ongoing effort to recapitulate the tumour microenvironment as closely as possible. “The big fantasy is to ask the question: can they serve as patient avatars?”

Taylor hopes that by growing the different cells together in a dish that fully emulate a patient’s tumour, they might be able to predict how the cancer might respond to treatment. This information could then fed back to the doctors, who can make informed decisions based on this new data. “How realistic this is we’ll have to wait and see,” says Taylor.

As amazing and inspiring as the science is, the big motivation behind this project is people living with ovarian cancer.

Ovarian cancer is sixth most common cancer in women in the UK, with a frustratingly small number of targeted therapies and an often challenging prognosis.

“One of the things about ovarian cancer is that it tends to develop silently, for quite a long time. So by the time women come to the clinic, the disease is already well advanced. That then obviously makes it difficult to treat,” Taylor comments.

And of course, without the consent of these patients, this kind of boundary-pushing research wouldn’t be possible.

“Taking on big challenges, like trying to find new treatments for cancer, requires big teams,” says Taylor. “This project has involved scientists, doctors, surgeons and pathologists. But the patients are part of that team as well. Without their commitment to research, without their samples, we wouldn’t be able to make the discoveries that will benefit future generations.” 

Lilly

    Comments

  • Elaine Bailey
    29 March 2020

    This is such an interesting article. My mother died of ovarian cancer and for me it is so very encouraging that projects like this are happening. One day I hope that this research will bring about more effective treatments and possibly even a cure so that other families do not have to watch their loved one suffer.

  • Susan Hickey
    19 March 2020

    This is wonderful work. my dearest friend in the whole world has stage four overran cancer at the present moment… It is not easy for her at all. Yet she is a real fighter and it is she who put this post up. Please keep up this excellent work… 💚

  • Julie Fiske
    17 March 2020

    Amazing work, never stop please. I lost my precious mum to this awful cancer and the look on her face when she was diagnosed will haunt me forever. I now have a little daughter and hope all your hard work helps her should she need it. Thank you.

  • Sue Bywater
    9 March 2020

    it is wonderful what research can do to understand cancers . More knowledge means that we will have a cure for this terrible illness. Power to the researchers.

  • Annie Batty
    9 March 2020

    This is such an interesting article, full of very necessary information that will help ladies to understand what happens to them during the progress of this distressing disease, and the enormous strides being taken to help to treat it.

  • Peter Wallis
    8 March 2020

    Thankyou for the research you are doing into this terrible disease,my wife Ann died of ovarian cancer it was painful to see,it was just a year from being diagnosed to dying,I am so grateful that you are trying to eradicate it.Pete.

  • Peter Wallis
    8 March 2020

    Just to say a big thank you for the research into ovarian cancer,sadly my wife Ann died of this 10years ago and did not show any symptoms,she also had several litres drained from her stomach,it was just a year from being diagnosed to dying,after having several sessions of chemotherapy,which on hindsight she would have had a better quality of life,without all the bad side effects of the chemotherapy, Pete.

  • Dinah Lewis
    8 March 2020

    Having incurable ovarian cancer any research and developments to treat this cancer is welcome.

  • Wendy Smith
    8 March 2020

    Fascinating work and so good to know about work being carried out on this cancer. Just recovering from my second bout of this dreadful cancer!! March is Ovarian Cancer Awareness month but unfortunately there is very little publicity – it really should have a higher profile. Keep up your wonderful work and thank you so much.

  • Ann Hunt
    8 March 2020

    An interesting, informative article. I genuinely respect and admire the clinicians who carry out this type of research and eventually find cures or treatments for many illnesses.
    My body is donated to medical research and I hope I can contribute in some way after death.

  • Alex Coppock-Bunce
    8 March 2020

    Very interesting. I wonder if low grade serous carcinoma ovarian cancer is also being investigated using this approach.

  • Geraldine taylor
    8 March 2020

    This is wonderful news. I have had ovarian cancer 6 years on i am still here which is great. But am worried that it will return. Have now been discharged from hospital but it would be better if they could check us once a year

  • Michelle Howarth-hynes
    8 March 2020

    This is brilliant, ive gotta go for a scan on my breast but that’s not the same is it, or it. Anyway just think u guys are doing a brilliant job x

  • Valerie F Hodgkinson
    7 March 2020

    I have just been discharged from the Christie 13 years and 1 month after I had an operation to remove my ovarian cancer. This research is so important and makes such a big difference to treatments etc.to me these researchers and the staff at Christies are saints.

  • Maureen Mellows
    7 March 2020

    Having had throat cancer in 2018 I know what to say to people suffering and that is positive thinking about recovery…I think attitude helps such a lot and at 77 I am so fortunate to be able to speak on the subject ..I also donate to Cancer Research as a thank you for saving my life as I was Stage4.

  • Mary Townsend
    6 March 2020

    Such a interesting article to read, & what wonderful dedicated research teams we have working on all types of cancers. God’s speed to you. I hope the day will come when this terrible disease is eradicated. Good luck & best wishes to you all.

  • Victoria Wilson
    6 March 2020

    I just read this article which brought tears to my eyes. I lost my mother to advanced ovarian cancer in 2014 having held her hand through every painful day of an 18 month illness. We hear so much about the other cancers but ovarian cancer is not at the forefront of the media and it should be because to my mind it is one of the very worst. I am in awe of this amazing team and would like to know if they accept charitable donations? I am considering a personal physical challenges to raise money but it is so important to me that the money goes to a cause that is worthy and this is the very one. Please let me know. My thanks to and admiration of your incredible team

  • carol douglass
    5 March 2020

    This was very interesting to read. My mum passed away from ovarian cancer in 1986. age just 52. she had good health and was never sick..her stomach swelled up it was awfull.. i would take part in any ovarian trials should I be asked.

  • Sally jolley
    26 February 2020

    Excellent reading so interesting thank you

    Comments

  • Elaine Bailey
    29 March 2020

    This is such an interesting article. My mother died of ovarian cancer and for me it is so very encouraging that projects like this are happening. One day I hope that this research will bring about more effective treatments and possibly even a cure so that other families do not have to watch their loved one suffer.

  • Susan Hickey
    19 March 2020

    This is wonderful work. my dearest friend in the whole world has stage four overran cancer at the present moment… It is not easy for her at all. Yet she is a real fighter and it is she who put this post up. Please keep up this excellent work… 💚

  • Julie Fiske
    17 March 2020

    Amazing work, never stop please. I lost my precious mum to this awful cancer and the look on her face when she was diagnosed will haunt me forever. I now have a little daughter and hope all your hard work helps her should she need it. Thank you.

  • Sue Bywater
    9 March 2020

    it is wonderful what research can do to understand cancers . More knowledge means that we will have a cure for this terrible illness. Power to the researchers.

  • Annie Batty
    9 March 2020

    This is such an interesting article, full of very necessary information that will help ladies to understand what happens to them during the progress of this distressing disease, and the enormous strides being taken to help to treat it.

  • Peter Wallis
    8 March 2020

    Thankyou for the research you are doing into this terrible disease,my wife Ann died of ovarian cancer it was painful to see,it was just a year from being diagnosed to dying,I am so grateful that you are trying to eradicate it.Pete.

  • Peter Wallis
    8 March 2020

    Just to say a big thank you for the research into ovarian cancer,sadly my wife Ann died of this 10years ago and did not show any symptoms,she also had several litres drained from her stomach,it was just a year from being diagnosed to dying,after having several sessions of chemotherapy,which on hindsight she would have had a better quality of life,without all the bad side effects of the chemotherapy, Pete.

  • Dinah Lewis
    8 March 2020

    Having incurable ovarian cancer any research and developments to treat this cancer is welcome.

  • Wendy Smith
    8 March 2020

    Fascinating work and so good to know about work being carried out on this cancer. Just recovering from my second bout of this dreadful cancer!! March is Ovarian Cancer Awareness month but unfortunately there is very little publicity – it really should have a higher profile. Keep up your wonderful work and thank you so much.

  • Ann Hunt
    8 March 2020

    An interesting, informative article. I genuinely respect and admire the clinicians who carry out this type of research and eventually find cures or treatments for many illnesses.
    My body is donated to medical research and I hope I can contribute in some way after death.

  • Alex Coppock-Bunce
    8 March 2020

    Very interesting. I wonder if low grade serous carcinoma ovarian cancer is also being investigated using this approach.

  • Geraldine taylor
    8 March 2020

    This is wonderful news. I have had ovarian cancer 6 years on i am still here which is great. But am worried that it will return. Have now been discharged from hospital but it would be better if they could check us once a year

  • Michelle Howarth-hynes
    8 March 2020

    This is brilliant, ive gotta go for a scan on my breast but that’s not the same is it, or it. Anyway just think u guys are doing a brilliant job x

  • Valerie F Hodgkinson
    7 March 2020

    I have just been discharged from the Christie 13 years and 1 month after I had an operation to remove my ovarian cancer. This research is so important and makes such a big difference to treatments etc.to me these researchers and the staff at Christies are saints.

  • Maureen Mellows
    7 March 2020

    Having had throat cancer in 2018 I know what to say to people suffering and that is positive thinking about recovery…I think attitude helps such a lot and at 77 I am so fortunate to be able to speak on the subject ..I also donate to Cancer Research as a thank you for saving my life as I was Stage4.

  • Mary Townsend
    6 March 2020

    Such a interesting article to read, & what wonderful dedicated research teams we have working on all types of cancers. God’s speed to you. I hope the day will come when this terrible disease is eradicated. Good luck & best wishes to you all.

  • Victoria Wilson
    6 March 2020

    I just read this article which brought tears to my eyes. I lost my mother to advanced ovarian cancer in 2014 having held her hand through every painful day of an 18 month illness. We hear so much about the other cancers but ovarian cancer is not at the forefront of the media and it should be because to my mind it is one of the very worst. I am in awe of this amazing team and would like to know if they accept charitable donations? I am considering a personal physical challenges to raise money but it is so important to me that the money goes to a cause that is worthy and this is the very one. Please let me know. My thanks to and admiration of your incredible team

  • carol douglass
    5 March 2020

    This was very interesting to read. My mum passed away from ovarian cancer in 1986. age just 52. she had good health and was never sick..her stomach swelled up it was awfull.. i would take part in any ovarian trials should I be asked.

  • Sally jolley
    26 February 2020

    Excellent reading so interesting thank you