Season 5 Episode 6: Understanding Clear Cell Ovarian Cancer: A Conversation with Dr. David Huntsman

In this episode of the GOSH Podcast, host Sabine continues our rare cancer series with an esteemed guest, Dr. David Huntsman. 🌟🎙 Dr. Huntsman is a renowned pathologist and clinical molecular geneticist at UBC, as well as the Canada Research Chair in Molecular and Genomic Pathology. As the director of OVCARE, BC’s leading ovarian cancer research team, his groundbreaking work has helped shape the future of ovarian cancer prevention, diagnosis, and treatment. 

Join us as Dr. Huntsman shares his insights on clear cell ovarian cancer, the latest advancements in ovarian cancer research, and the role of the GCI. Don’t miss this expert discussion on the science driving new discoveries in cancer care! 

Resources:

Huntsman Lab - https://www.bccrc.ca/dept/mo/labs/huntsman-lab 

Donate to the Nancy McKinstry Endowment Fund for Ovarian Cancer at https://donate.bccancerfoundation.com/site/TR?px=2927503&fr_id=4394&pg=personal&s_src=LNY20

For more information on the Gynecologic Cancer Initiative, please visit https://gynecancerinitiative.ca/ or email us at info@gynecancerinitiative.ca

Where to learn more about us:
Twitter – @GCI_Cluster
Instagram – @gynecancerinitiative
Facebook – facebook.com/gynecancerinitiative
TikTok – @gci_gosh

Transcript

00:00:01 Intro 

Thanks for listening to the GOSH podcast—The Gynecologic Oncology Sharing Hub. We share real, evidence-based discussions on gynecologic cancers, featuring stories from patients, survivors, researchers, and clinicians. Our podcast is produced and recorded on traditional unceded territories of the Musqueam, Squamish, and Tsleil-Waututh Nations. It is produced by the Gynecologic Cancer Initiative, a BC-wide effort to advance research and care for gynecologic cancers. 

00:00:37 Sabine 

Hello, everyone! My name is Sabine, and I’ll be your host for this episode of the GOSH Podcast. Today, we dive deeper into our rare cancer series with an esteemed guest: Dr. David Huntsman. Dr. Huntsman is a pathologist and clinical molecular geneticist at UBC and is the Canada Research Chair in Molecular and Genomic Pathology. Dr. Huntsman directs OVCARE, BC's multidisciplinary ovarian cancer research team, and conducts his research at the BC Cancer Agency and Vancouver General Hospital. Dr. Huntsman's research has led to the development of diagnostic, predictive and prognostic tissue-based cancer biomarkers for ovarian cancer and a wide variety of other tumor types. His team has created a blueprint for subtype specific ovarian cancer control and have been leaders in the application of novel genomic technologies to better prevent, diagnose, and treat ovarian cancer. Dr. Huntsman is also a fellow of the Royal Society of Canada and the Canadian Academy of Health Sciences. He has also been awarded the prestigious King Charles III Coronation Medal. Today, Dr. Huntsman joins us for a researcher's perspective on clear cell ovarian cancer, and to share more about his work and the GCI. I hope you enjoy the episode! 

00:02:00 Dr. Huntsman 

Hello. 

00:02:01 Sabine 

Hi Dr. Huntsman. how are you? 

00:02:03 Dr. Huntsman 

Very well. 

00:02:04 Sabine 

Good. Thank you for joining. Thank you for taking the time to do this. 

00:02:09 Dr. Huntsman 

No, no, it's a pleasure. Should we jump right in then? 

00:02:13 Sabine 

Yes, definitely. So, can you give us a brief overview about clear cell ovarian cancer and how it differs from other types of ovarian cancer? 

00:02:25 Dr. Huntsman 

So, clear cell ovarian cancer is, in British Columbia, the second most common type of ovarian cancer. And it's histologically quite distinct, meaning that when you look down at a microscope, it looks very different from the other subtypes and that's because its biology is different. So, we call it clear cell cancer because the way we process cancer samples in the lab, which is to sort of pickle them in formalin, then to put them into wax blocks, cut thin sections, stain them with some natural dyes, and look at them down a microscope, the cells look clear. Of course, if you look at the cancer which came straight from the patient, it wouldn't look clear at all. But it is really an artifact of the way we process the samples. The reason why the cells look clearer is that the cancer cells are stuffed filled with glycogen, which is sort of a carbohydrate. It's an energy source and also lipids and fats. And so that would seem to indicate that the metabolism or the way these cells use energy is very different from other cell types. And clear cell cancers as they are much less common than the most common type, high-grade serous ovarian cancer. And so, they have received much less attention. They don't tend to respond to standard treatments. And This is why Treatments or new ways of preventing patients needing treatments are urgently needed. 

00:03:57 Sabine 

Yeah. And who is most at risk for clear cell? 

00:04:01 Dr. Huntsman 

So clear cell cancer and endometrioid carcinoma are strongly associated with endometriosis of the ovary. Now I must add that the vast majority of women, I can say almost all women who have endometriosis, will not get this cancer. The cancer is quite rare. It's about 10% of ovarian cancers. It usually comes from endometriosis of the ovary and for reasons we don't understand, not endometriosis in other places.  

00:04:34 Sabine 

Okay. And what do we currently know about the risk factors related to clear cell ovarian cancer. 

00:04:44 Dr. Huntsman 

For most cancers, age is a risk factor. Endometriosis would be the next big risk factor. And there are other major risk factors. 

00:04:55 Sabine 

Okay. And what are some of the biggest challenges in diagnosing and treating this type of cancer?  

00:05:03 Dr. Huntsman 

So, the diagnosis is actually not difficult. Ever since this cancer has been recognized as being a different entity. To diagnose this, pathologist haven't had much trouble making because it looks so different, even very different from the other cancer which comes from endometriosis, called endometrioid carcinoma, which is really like a cancer of the uterus but in the wrong place. So, the challenge isn't to the diagnosis. Now, many patients present at an early stage, meaning that the cancer has not progressed outside of the ovary when the time they're diagnosed. If that's the case, surgery can often cure patients with clear sarcasm with the ovary because the tumor doesn't tend to spread around the abdomen the same way the common type, and it can be completely contained within ovary if picked up early. But if it's spread, it is difficult to treat because it does not respond to the standard treatments used to treat ovarian cancer. So, our group and others around the world are trying to develop new ways of treating this cancer because that's really needed. 

00:06:08 Sabine 

Okay. And what do you think is the biggest unanswered question or questions in clear cell ovarian Cancer Research right now? 

00:06:20 Dr. Huntsman 

Well, I think the clear cell carcinoma is all about really the question will be what is the optimal treatment. What is the treatment that can prevent death from this cancer, and create, you know, a life, you know, to celebrate after treatment? So less toxic treatments which work better for this cancer. 

00:06:45 Sabine 

Yes. And can you share with the listeners what your research team studies specifically? 

00:06:53 Dr. Huntsman 

So, I've been working with the ovarian Cancer Research team and was part of its inception and Has led its research since. And seen it expand and grow and then become part of the much larger initiative, the Gyne Cancer Initative, which has a broader vision and includes other gynecologic cancers and also has much more of a population-based mandate. So, I'm very proud to see this expansion of what we do, the new team members have come in different types of research we are trying to embrace. And I'm trying to help and encourage all those working to try to attain our goal of decreasing death and suffering from these cancers by 50%. My own research has shifted from the identification of the key changes in DNA that underpin the development of ovarian and other gynecologic cancers to really trying to dig into how these cancers happen. And finding mutations isn't enough to explain cancer 'cause we often find the same mutations in normal tissues. So our group use cancers has been the product of interactions between cells of origin, or where this starts, the mutations and other changes in DNA, and where the cancer is arising. And because very similar looking tissues in different parts of the body have very different tolerances to having different the same mutation. And so, we're trying to get into the middle of this. This idea that every type of cancers are distinct endpoint of an oncogenic journey which has a start, a cellular origin, a mutation, which is what happens along the way, and a microenvironment, which is the terrain where this happens. So, it's like a hike, and if you change any of those three things, you end up at a different place. 

00:09:03 Sabine 

Okay. And how does your research translate to real world treatment options for patients? 

00:09:09 Dr. Huntsman 

Yeah. So, that type of consideration, if you think about, you know, where things start, that led to opportunistic salpingectomy. And we're trying to further develop that idea like why do things actually grow in the ovary in the first place? We don’t know. Why don't things like to grow in the fallopian tube? And, in terms of mutation, some are cancer, particularly rare cancers have very, very specific mutation types. And we found some of those mutations, but we're trying now to develop the models so we can really understand why and the hope of developing new treatments. When people think of microenvironment, usually they immediately start thinking about immune cells. That's obviously important in terms of how you can treat some cancers. But, where the cancers go beyond the immune cells, the microenvironemnt is really important. We believe this specific microenvironment of endometriosis on the ovary, which is a cyst, which is filled with blood and old cellular debris, is a very toxic microenvironment and the cells which can survive in that microenvironment are kind of hardened and can survive anywhere, and if those cells are mutated, what you get is a clear cell cancer and that is the approach we're taking to studying colossal cancers, and we've drawn quite a lot of insights, including the identification of some really interesting targets for new drug development for this or cancers, by taking that approach. 

00:10:46 Sabine 

That's very interesting. In our previous podcast episode, I had the pleasure of interviewing Nancy Mckinstry, who has clear cell ovarian cancer. 

00:10:56 Dr. Huntsman 

Oh my gosh. That must have been an honour. 

00:10:57 Sabine 

Yeah, it was wonderful. 

00:11:01 Dr. Huntsman 

An incredibly impressive person. 

00:11:03 Sabine 

Yeah. And I wanted to know how it was for you to work with her and her journey from, you know, patient to patient-partner. 

00:11:12 Dr. Huntsman 

When you do research, particular research as part of a team, you work with the public in many different ways. The end result of your research, you hope, is a change in the health of the public. So, you hope that the ultimate beneficiary of your work are the general public. Also, we obviously work with the public in terms of fundraising, and we couldn't do any of the things we do without the support we receive. When Nancy Mckinstry joined us she immediately took on a very different role. It went way beyond somebody to discuss research ideas, somebody who we would communicate with, perhaps I get help with fundraising from, to somebody who became an inspiration for the whole team, but also who educated us and helped us develop our strategic priorities. And throughout Nancy's career, which has been a massively successful career in business in Vancouver, she mentored many of the female business leaders in British Columbia. And she did the same did the same amazing mentorship to several of our team members as well, but we all benefited from working with her because she had wisdom and perspective we lacked. 

00:12:37 Sabine 

Absolutely. And it seems that philanthropy has really shaped the work that's been done in OVCARE, and especially with Nancy's endowment fund. What does it mean to you that the endowment fund also had prizes for trainees, that it supports the next generation of researchers? 

00:12:57 Dr. Huntsman 

Well, in research the future is all that counts. What’s happened in the past is done. You build from. It's past accomplishments where we work from, not towards. And so, the trainee awards are fantastic. And these awards allow us to provide trainees with something which is much more like a living wage. I mean, I don't think the general public realizes, but when people go into graduate studies, they're often the smartest people in their classes, and they could be 24 years old, if they’ve done really well in their undergraduate degree, they've gone through competitive processes going to a PhD program, and they're not given enough funds to get by. It’s impossible in Vancouver without sharing a 1 room flat with three other students and stuff like that. So, these scholarships allow us to make going into graduate studies sensible for smart people who want to A difference. 

00:14:05 Sabine 

Yeah, absolutely. And final question which is related to OVCARE is when it started, when it first began, how do you feel about where it was and where it is? What were your goals for it originally, and you know, how do you see has it progressed? 

00:14:26 Dr. Huntsman 

Yeah, I think about that a bit. I'm sort of rounding third base on my career, or maybe I've gone past it already, and shifting my focus towards mentorship and trying to build for the future so others can have a greater impact than I've had. When we started OVCARE, our ambitions were very humble. We hadn't seen great examples of the power of teamwork in our environment. And I in no way could I have dreamt that we would have had the impact we've had. I go around the world and I meet different teams and some of them are doing basic research we could never dream of, or clinical trials in ways that I'm quite envious of or they do other things really well, but I wouldn't trade the impact our team has had in ovarian and gynaecologic cancers at large with the work of any other group in the world. And there's no way I could've predicted that happened. It was the power of teamwork. It was also .. I mean, there are things we can be proud of, but it was also like with anything in life, there's stuff you can own and there's stuff which is dumb luck and you just have to celebrate and be grateful. Diane Miller, who inspired us to work together as a team, myself and Blake Gilkes, could work so effectively for so many years and share the same ideals in terms of it not being about us, it was about the team, allowed it to happen. Otherwise it would have broken. And we also had a very strange thing happen when we started, where the beginning OVCARE, the sort of idea of public access publishing, was just sort of taking hold. And it seemed like such a good thing at the time. We didn't anticipate that that would lead to predatory journals which are sending everyone horrid emails and causing all sorts of issues. It looked like a great idea. And so we were really inspired by it. And the first OVCARE meeting, there are quite a few people around the table, some of whom were probably proven extremely difficult to work with. But we made this policy that any data which was derived using OVCARE funds would be a team asset, would be team property. And it turns out people who are difficult to work with don't like to share. And so, the next time we had a meeting, it was a beautiful group of people who wanted to work together, wanted to share things. And that was the platform we built from. And that was not by design. We kind of lucked into. That was us stumbling around, figuring out how we're going to build a team and somehow striking gold. The shift from OVCARE to the Gyne Cancer Initiative was a kind of natural change because we started to focus more on endometrial cancer and you can't study ovarian cancer without thinking of the uterus and the fallopian tube. And we have brilliant researchers studying cervix cancer prevention, and some of our new recruits are leading the way in trying to improve the management for cancer, the vulva. And so, we were much more of an OVCARE long before we kind of started calling ourselves the Gyne Cancer Initiative. But it provided us a way of projecting more into the community. And it's hard to say where it all ends and the Gyne Cancer Initiative begins, and whether OVCARE even exists as an independent entity at this point. The most important thing is we do share a mission and that mission is expanded. So, it's what we do in Vancouver. We have to come up with solutions which can impact everyone across the population. That's the only way we can achieve our goal of decreasing death and suffering from these cancers by 50%. 

00:18:30 Sabine 

Yeah, absolutely. It's extremely impressive and lovely to see where it's going. 

00:18:35 Dr. Huntsman 

You're part of this. 

00:18:38 Sabine 

I'm trying to be. 

00:18:41 Dr. Huntsman 

Yeah, we want this to be an open platform and open community. We don't know whether you know the next big idea is going to come from or the next person who's going to drive another shift in how we do things. We try to cast the net widely and try to create an environment where as many people as possible can participate. 

00:19:04 Sabine 

Yeah. Thank you so much. Those are all the questions I had. Is there anything else you want to add? 

00:19:11 Dr. Huntsman 

No, just really thanks for doing this. 

00:19:13 Sabine 

Yeah, for sure. 

00:19:14 Dr. Huntsman 

Yeah, this stuff is really much more important, I mean, as you probably realize, it's great that going to do this with a patient, but sadly it didn't work out, but it's Probably for as long as you've been doing research, it looks like there's been patient partners. But this is actually a very new thing and community of figuring out how to make it work. And there's been stumbles along the way where either sometimes people were asking patient-partners to do things which just didn't really make sense, like reviewing very technical grants and stuff. But you know, idea Co-development and you know and things like this and having patient-partners engaged in training and maximizing exposure with trainees, and working on translation advocacy, all are really important and you know it's, you know, this is a big part of the future. And since It's always been around for you, you're probably way better at it than I am. 

00:20:23 Sabine 

No, I mean it's so great to talk to patients. This job has allowed me to do it way more and it's just nice to see where what we're doing is going. 

00:20:36 Dr. Huntsman 

Excellent. Okay. So yeah, well, thanks for doing this today. 

00:20:42 Sabine 

Thank you for joining. 

00:20:45 Outro 

Thanks for joining us on the gosh podcast to learn more about the Gynecological Cancer Initiative and our podcast, make sure to check out our website at gynecancerinitiative.ca