Fast-tracking pediatric cancer care

Dr. Georgina Barnabas and PhD candidate Tariq Bhat — from the Lange and Lim Labs at BCCHR — share how they used proteomics and a personalized tumour model to identify a treatment option for a child with hard-to-treat cancer, within just two weeks. 

Their story reveals how the latest precision approaches are identifying hidden vulnerabilities in aggressive childhood cancers and reshaping what's possible when conventional cancer treatments fail. It's a glimpse into a future where researchers and clinicians can respond as quickly and as personally as each diagnosis demands.

Learn more about topics discussed in this episode:

ACCESS website

BRAvE website

PROFYLE website

Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe, EMBO Molecular Medicine

All episodes written and produced by the Research Communications team at BC Children's Hospital Research Institute.

Theme music: "Life Is Beautiful" by Anastasia Kir

Transcript

Kristen Hovet (00:00)
My name is Kristen Hovet, and I'm a research communications specialist for BC Children's Hospital Research Institute. Joining me today are Dr. Georgina Barnabas and Tariq Bhat. Dr. Barnabas and Mr. Bhat co-first authored a research article titled, "Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe," published in April 2025 in the journal EMBO Molecular Medicine.

Georgina Barnabas (00:31)
Hi, I'm Georgina Barnabas. I was a postdoctoral researcher in BC Children's Hospital Research Institute in Dr. Lange's group. My main focus was to identify actionable targets in hard to treat or rare pediatric malignancies using proteomic approaches. Currently, I'm a molecular pathology scientist at Vancouver General Hospital, where I'm involved in developing and validating new diagnostic assays to improve cancer detection.

Tariq Bhat (00:58)
Hi, my name is Tariq Bhat and I'm a final year PhD candidate in the Lim Lab at BC Children's Hospital. Currently I'm wrapping my thesis. My research focus is on evaluating targeted drug therapies in pediatric solid tumours using the CAM model, which we are discussing today. So CAM basically is chorioallantoic membranes, also known as chick egg model as a xenograft system. So this is my area of research currently at BC Children's Hospital.

Kristen Hovet (01:27)
Thank you. And this is a really interesting study that we're talking about today in that it's focused on one patient. And your team decided to report the findings early to encourage similar approaches when a pediatric cancer is recurrent or hard to treat. Can you tell us a bit about the patient's cancer?

Georgina Barnabas (01:46)
So this is a rare, slow-growing malignancy that primarily affects adolescents. So it has an approximately more than 80% of five-year survival rate, but it also carries a significant risk for recurrence and metastasis. So this makes this cancer particularly challenging to treat or to manage. And also I would like to mention that it's a rare tumour, so there is limited literature and clinical guidance that is available. So this further complicates the decision-making process in relapsed cases.

Tariq Bhat (02:19)
As Georgina already highlighted, the thing that it has a five-year survival rate, which has more than 80% survival. But the thing is that we still have like 20% population which is awaiting for potential therapeutics for these type of cancers and the very, you know, kindness of the resistance or the refractoriness of this tumour, as mentioned already by Georgina that because this tumour has a slow potential of metastasis. So that also kind of, you know, leads it to a non-therapeutic avenue where we don't have therapies to treat these types of cancers. 

And I also would like to highlight that this tumour, as this is an adolescent tumour, it had three relapses even after being treated with the conventional therapy and also used a tyrosine kinase inhibitor, but it didn't respond. So these kinds of tumours sometimes, even though we have 80% of survival rates, but the rest of the population, 20%, we still don't have effective therapies available.

Kristen Hovet (03:19)
I understand that your patient's cancer is rare, but their experience, as you were mentioning, is still representative of many children who experience cancer. So even with all the advances that have taken place in pediatric oncology, what are the main challenges in treating recurrent or advanced childhood cancers?

Tariq Bhat (03:41)
I think there's a bunch of reasons for that. So one of the foremost bunch of things are that we don't have availability of targeted drug therapies as we have for adult tumours. The reason being that these tumours, they're biologically complex and the heterogeneity between the childhood cancers is different than adult tumours. 

And apart from, as we mentioned, the metastasis thing, and then the resistance comes in place, we don't have a sufficient sample size from the pediatric cancers. There are a lot of reasons for that. Sometimes we don't have family consensus on those things. And then the identification of a valid target or molecular target is also kind of a hindrance or a challenge in targeting these type of cancers. Then apart from these things, we also have, like within the countries or within the world, we don't have data sharing openly. There are systems now in place which are coming. Patients' privacy, limited availability of biopsies in the different clinical settings also kind of make a challenge to treat these kinds of cancers.

Georgina Barnabas (04:45)
I just wanted to mention that there's also long-term toxicity and side effects when we identify and validate these targets. So that's also one of the major challenging points.

Tariq Bhat (04:56)
Yeah, as Georgina mentioned, the toxicity, you know, these are small kids and we usually use conventional therapies. So we also have to think about the toxicities attached to those conventional therapies. So when we talk about conventional therapies, it's like chemotherapy is usually what we have available. And then these kids being small and, you know, in terms of their immunity and in terms of their tolerance, it leads to the toxicities. That's why we need therapies which are really, really specific to those tumours and that will only affect the cancer cells, not the normal cells. So that's also kind of an hindrance in terms of not having the targeted therapies available or we don't have immunotherapies available for these kids. Being treated with conventional therapies, their immune system gets weak. So we are also devoid of immunotherapies for these types of cancer.

Kristen Hovet (05:50)
Thank you. Yeah, that makes sense. So your research combined proteomics with personalized tumour models. For those unfamiliar, can you explain both of these in simple terms and the ways they can help reveal treatment options?

Georgina Barnabas (06:04)
Proteomics is an approach to study all the proteins in a cancer cell. So we can see what proteins are there and what are the levels of each protein. So since these proteins drive the cancer cell growth, they also contribute to drug resistance and also eventually the cell survival. By analyzing a tumour's protein profile, we can see which cellular pathways are activated in a particular cancer type. 

So for example, if they are involved in growth signals or repair mechanisms, we can see which pathways are active and we can also identify actionable targets that might be suitable for a tumour. And we can also understand more about the tumour's molecular profile.

In this study, we used proteomics to identify a target, which is SHMT2. And further on, because we wanted to know if we could validate this target for this particular malignancy. So for that, we collaborated with Dr. Lim and with Tariq to develop a personalized tumour model using chicken egg and we followed up on drug response studies to validate the target. I think Tariq can add a bit more on the personalized model approach.

Tariq Bhat (07:11)
To add on this, as Georgina already mentioned of the proteomics, the study of proteins, then we collaborated this kind of finding with a personalized model. So which is very crucial for any type of research, particularly when we are doing the childhood cancer research. So we need a model where we can use it very effectively. In this case, what we have here in BC Children's in the Lim Lab, we have a chicken egg model.

As I mentioned previously, it's a chicken egg model. It's also called a chorioallantoic model. Basically, these are fertilized chicken eggs. They have the membrane which we use for implanting those tumours. The CAM model is basically a robust model, very cost effective, easy to handle, simplified in vivo model for developing or for growing these childhood tumours in those. I'll go further on this, what exactly we do.

So this model actually is an alternative to the mouse model, which conventionally people use in laboratories. Being an alternate model or being a complement model to the mouse, this kind of bridges the gap between the in vitro studies, the studies which we do initially on some biochemical reactions, or then we go to the complex model systems. So this comes in between. So we don't have to have big facilities to use this model. It can be done in a simplified way.

The important thing in this model is that it takes just one week or two weeks to complete the study in this model. This is in comparison to the mouse, which takes like three months, four months to get the tumour developed and then evaluate the targeted therapy or any kind of therapy on those tumours. So this gives us a platform in a simplified and in the short term to evaluate these types of tumours, which are crucial for clinicians or for the families or the patients to get to know or to have some treatment available, which is kind of resistant for, you know, for conventional therapy. 

So what we do here is that we basically replicate the tumour on the chicken egg membrane. This kind of a method allows in growing a small piece of the patient's tumour on the chicken egg. And then this serves as an avatar or a host for the tumour, the patient tumour. 

And then once we identify some targets in those tumours, as Georgina mentioned, in this approach, we used proteomics. Okay, we got SHMT2. And then because now we have this patient's small tumour on this avatar, which is chicken egg, we use a personalized treatment therapy and check these therapies on those avatars, which is personalized for that particular patient, which was not responding.

So just to highlight here that this chicken egg is also a BRAvE initiative at BC Children's, which helps us to connect between the clinicians as well as to connect our research labs within the BRAvE.

Kristen Hovet (09:58)
Interesting. Thank you. And can you explain what BRAvE is for those who may not know?

Tariq Bhat (10:03)
Yeah, so BRAvE basically it's an initiative at BC Children's, it's Better Responses through Avatars and Evidence. So when we say better response, so we want those patients who don't have therapies available or the therapies which are not working, we need some therapy for them. So we are using these kinds of avatars. So avatars here is like CAM, this is an avatar for that particular tumour. And then we produce those avatars and have some evidences on that. So basically Better Responses through Avatars and Evidence.

Kristen Hovet (10:32)
And as you mentioned, you identified a target within two weeks of the patient's biopsy, which is incredibly fast, as you mentioned, compared to the three months of other models. And you also talked a little bit about why that speed is so critical. So is there anything you wanted to add about why speed is critical in these types of situations?

Georgina Barnabas (10:52)
One thing is if the disease is aggressive, so in relapsed or advanced pediatric cancers, the tumours can grow and spread rapidly. So there is often a very small window of time to intervene. And also these patients have often exhausted conventional treatments. So finding an alternative fast option could mean the difference between stabilizing the disease or losing the opportunity to treat becomes lesser. I think these are the critical reasons why the speed is important and maybe Tariq can add more points to it.

Tariq Bhat (11:22)
Perfectly highlighted by Georgina. So apart from that, like we need a model, as we discussed in the previous section, that we need something which is fast. So here the CAM is a fast model. So it takes just a week or two weeks to complete the study. So when we identify the target, we need some model where we can evaluate these faster because we need to inform those things to the clinicians for devising or introducing some drug to the patient. So that's why this time becomes very critical for us.

Kristen Hovet (11:52)
In your study, you used a common antidepressant medication called sertraline to target the increase in an enzyme, as you mentioned, called SHMT2. Can you walk listeners through this process of repurposing sertraline as a treatment option for your patient?

Georgina Barnabas (12:09)
We initially found SHMT2 as a target from proteomic studies, and then we validated the drug response in the chicken egg model. And while we were doing the study, we also, this is the next step, what we thought was, now we need to find the relevance. We need to find if there is an available drug to inhibit the SHMT2, then this would be a perfect target for this malignancy. 

So we did a literature review, and then we found that there was a recent publication that talked about repurposing antidepressant sertraline that showed that it could target tumours that have high SHMT2. And that looked like a perfect fit for us. So we went on and purchased the drug and then we wanted to validate this on the personalized tumour model. 

And more importantly, sertraline is an already existing medication and it is approved to use in kids. Since a lot of medications are not approved for kids and they are mostly to use in adults only. So this came in as a very good opportunity for us to move forward and test it. And this allowed us to use sertraline as a treatment option.

Kristen Hovet (13:10)
For people listening, I do want to make sure that they don't think that they can treat or avoid getting cancer by taking these types of medications. So I'd like to make it really clear why this particular medication worked for the particular vulnerability you found in the tumour, if you could explain that.

Tariq Bhat (13:29)
Once we found out that SHMT2 is a protein which was really high in this patient's sample, and then we wanted to look for some targeted drug therapy for this patient. And while looking in research on that, we found this drug, sertraline, the antidepressant, because sertraline also inhibits this type of protein. 

So it's not that we can use the antidepressant drug for any type of cancer, because in this particular tumour, we identified this protein because sertraline has kind of a mechanism where it inhibits this protein. As this was already reported that sertraline inhibits this protein, that's why we found out, okay, we should use this in this particular type of patient because it already had this protein activation. I think that becomes crucial. It's not that it's like a globally... can be used for any type of treatment. Also, you know, because we didn't stop there as the patient started showing the resistance and the conventional therapies failed.

We were looking for something, we were looking for something, okay, can we do something on this type of cancer or this patient? And that's how we identified this tumour has a metabolic reliability on this protein. And as already mentioned, sertraline is already approved, so it was easy for us to use it. Otherwise you need really clinical registrations to go ahead. 

I think in a simplified way or simplified conclusions, no, we cannot use any type of antidepressant for any cancer. No, it was a target-based therapy here used where sertraline has a role.

Kristen Hovet (14:55)
I know that this repurposing of drugs is happening a lot. What are other classes of drugs, for example, that are being used in this same type of scenario?

Tariq Bhat (15:05)
It depends on the research or the patient they are looking for. But we know that there's a lot of research going on where people are trying to use these approved medications for some sort of cancers. But we know there are a lot of repurposing research [studies] going on, the drugs which are already approved, if they are safe or they are already approved for the children or they're already approved for large populations.

Georgina Barnabas (15:28)
This drug called metformin... so initially it's meant for type 2 diabetes, but this can also inhibit the tumour growth and is used for mTOR inhibition. And it's mainly used in breast and pancreatic cancers. So just to add to Tariq's point, just to give an example.

Kristen Hovet (15:46)
That's really interesting. This research was part of the PROFYLE program, which helps young people across Canada with advanced cancers. How is PROFYLE changing the way we approach precision medicine in pediatric oncology?

Tariq Bhat (15:59)
This work was a collaborative effort by PROFYLE. PROFYLE is PRecision Oncology For Young peopLE. It's a key initiative of ACCESS, A-C-C-E-S-S, Advancing Childhood Cancer Experience, Science and Survivorship. This is the first time in Canada that more than 30 pediatric cancer research institutes as well as funding agencies with more than 100 investigators are joining forces together under PROFYLE.

This is a pan-Canadian project to give children or adolescents and young adults who are out of conventional treatment options another option or a chance to beat their cancer. So it gives an opportunity for children across Canada, no matter where they live.

Kristen Hovet (16:45)
For families navigating a rare or aggressive cancer diagnosis or recurrent cancer, hearing about this kind of research can bring a lot of hope. What message would you want them to take away from this patient's story and your team's work?

Georgina Barnabas (17:00)
For families facing this rare or aggressive cancer, I can understand the road can be very isolating and overwhelming, but I wanted to emphasize that there is a path to move forward, even when the cancer is rare or it comes back. There are dedicated teams like PROFYLE, ACCESS, they are across Canada, they are working to uncover new options, new targets, to give hope to all these families. 

And with every study, we also gain a lot of experience as we push forward our research projects. We also are getting closer to the day where we can say, oh, any family can approach cancer without having any questions in their mind. With these programs, it also allows us to deeply profile a child's tumour beyond the standard test that's available. And we can also discover the vulnerabilities that each tumour has. And we can use these models to find actionable targets.

Tariq Bhat (17:54)
Definitely, yeah, it brings hope not only for the families or the communities, but also for the research fraternity at large. Because when we have all these agencies or organizations within one umbrella, it becomes easy for all the researchers to work on some particular case and then identify the vulnerabilities and just see what was easy, what is difficult in going ahead as a treatment. 

And then, because now it's a national platform throughout Canada, for the clinicians and the researchers to know what kind of tumour it was and what was the way they handled it. And when those kinds of treatments are available or there is some kind of hope, that makes the families at least a little relaxed. Okay, so there is something going on which is hopeful for all of us, not only just the families.

Kristen Hovet (18:42)
For sure, definitely. And what excites you most about where your research is headed next?

Tariq Bhat (18:49)
I think the most exciting part about the research is when it has a direct impact on society. The kind of work which we are doing when we work in BC Children's Hospital and the research labs [there], we know we are not just doing some research which takes a lot of time to get implemented in the clinical settings or for the patients. We know what we are working on every day has a direct impact for the patients, for the families, for the communities around.

This itself gives us kind of push, like, you're doing work which is [necessary]. And you know, these results are really helpful. I mean, when we do all this research, we know this is going to translate into clinical practice or actions. So that feels good.

Georgina Barnabas (19:30)
I think you pretty much covered what I wanted to say that we're able to identify real-time targets. We can uncover vulnerabilities and we can also learn along the way. That's more important.

Kristen Hovet (19:42)
Thank you so much. I have one more question. So we're asking this because the podcast is Best Lives. We're asking all podcast guests, how does your research help children live their best lives?

Tariq Bhat (19:53)
Every child with cancer deserves the best possible care, no matter who they are or where they live. And that's how all these bodies are there, the organizational bodies. The mission behind ACCESS we have right now in Canada is that, being a national program, we have all the experts there, we have children's hospitals, we have charities, we have families working together to improve the lives of young cancer patients.

I think that's something which motivates every researcher, every clinician: we are not alone. Families are not alone. We are all together. We are working on the same mission. One of the key parts of the ACCESS is like, as in PROFYLE as an initiative: We identify those cancers or actionable targets and then those can be used for effective treatments for each child.

Georgina Barnabas (20:44)
I just wanted to emphasize what you said. Like for families, we wanted them to know that the team is fighting beside them. We have many programs in the lab or in the clinic or across the country to turn our research into real and personalized hope. So we are working, helping kids get back to being kids and not just surviving cancer, but thriving beyond it.

Kristen Hovet (21:05)
That's amazing. Thank you so much.

Tariq Bhat (21:08)
I think I will add the last point, I think a strong belief within the community and the collaboration is important: tackling childhood cancers, it takes all of us. It's not just one. We all are there, together.